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

Bile acid receptor

Gene

NR1H4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 homoestasis 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:12660231, PubMed:12554753, 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 a anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).By similarity2 Publications28 Publications
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.1 Publication
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.1 Publication
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.1 Publication
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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei375 – 3751AgonistBy similarity
Binding sitei383 – 3831AgonistBy similarity
Binding sitei461 – 4611AgonistBy similarity
Binding sitei483 – 4831AgonistBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi134 – 20976Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri137 – 15721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri173 – 19725NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • bile acid binding Source: BHF-UCL
  • bile acid receptor activity Source: UniProtKB
  • chenodeoxycholic acid binding Source: UniProtKB
  • ligand-dependent nuclear receptor binding Source: BHF-UCL
  • peptide binding Source: Ensembl
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: UniProtKB
  • steroid hormone receptor activity Source: Ensembl
  • thyroid hormone receptor activity Source: InterPro
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: MGI
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription coactivator activity Source: ProtInc
  • transcription corepressor activity Source: ProtInc
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • bile acid and bile salt transport Source: Reactome
  • bile acid metabolic process Source: Ensembl
  • bile acid signaling pathway Source: BHF-UCL
  • cellular response to fatty acid Source: UniProtKB
  • cellular response to organonitrogen compound Source: BHF-UCL
  • cellular triglyceride homeostasis Source: UniProtKB
  • digestive tract development Source: Ensembl
  • histone H3-R17 methylation Source: UniProtKB
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • interleukin-17 secretion Source: UniProtKB
  • intracellular bile acid receptor signaling pathway Source: UniProtKB
  • intracellular receptor signaling pathway Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of bile acid biosynthetic process Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of interferon-gamma secretion Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • negative regulation of tumor necrosis factor secretion Source: UniProtKB
  • nitrogen catabolite activation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • Notch signaling pathway Source: Ensembl
  • positive regulation of ammonia assimilation cycle Source: Ensembl
  • positive regulation of glutamate metabolic process Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of bile acid biosynthetic process Source: BHF-UCL
  • regulation of carbohydrate metabolic process Source: Ensembl
  • regulation of cholesterol metabolic process Source: BHF-UCL
  • regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • regulation of low-density lipoprotein particle clearance Source: UniProtKB
  • regulation of urea metabolic process Source: BHF-UCL
  • response to glucose Source: Ensembl
  • response to lipopolysaccharide Source: Ensembl
  • signal transduction Source: ProtInc
  • toll-like receptor 4 signaling pathway Source: UniProtKB
  • transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor, Repressor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-159418. Recycling of bile acids and salts.
R-HSA-192105. Synthesis of bile acids and bile salts.
R-HSA-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-HSA-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-211976. Endogenous sterols.
R-HSA-383280. Nuclear Receptor transcription pathway.
SignaLinkiQ96RI1.
SIGNORiQ96RI1.

Chemistry

SwissLipidsiSLP:000001581.

Names & Taxonomyi

Protein namesi
Recommended name:
Bile acid receptor
Alternative name(s):
Farnesoid X-activated receptor
Farnesol receptor HRR-1
Nuclear receptor subfamily 1 group H member 4
Retinoid X receptor-interacting protein 14
Short name:
RXR-interacting protein 14
Gene namesi
Name:NR1H4
Synonyms:BAR, FXR, HRR1, RIP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7967. NR1H4.

Subcellular locationi

Isoform 1 :
Isoform 2 :
Isoform 3 :
Isoform 4 :

GO - Cellular componenti

  • nuclear euchromatin Source: BHF-UCL
  • nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

May be involved in intrahepatic cholestasis of pregnancy.

May be involved in cholesterol cholelithiasis.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi132 – 1321K → R: Abrogates SUMO1-medieated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-289 and A-291. 1 Publication
Mutagenesisi132 – 1321K → R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and SETD7. 1 Publication
Mutagenesisi145 – 1451S → A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-164. 1 Publication
Mutagenesisi164 – 1641S → A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-145. 1 Publication
Mutagenesisi167 – 1671K → R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, no effect on interaction with RXRA and SETD7. 1 Publication
Mutagenesisi220 – 2201K → R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, impairs interaction with RXRA and SETD7. 1 Publication
Mutagenesisi227 – 2271K → 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. 1 Publication
Mutagenesisi289 – 2891K → R: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and A-291. 1 Publication
Mutagenesisi291 – 2911E → A: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and R-289. 1 Publication
Mutagenesisi353 – 3531K → 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. 1 Publication
Mutagenesisi456 – 4561T → A: Impairs transcriptional activation of ABCB11/BSEP. 1 Publication
Mutagenesisi474 – 4741K → R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and impairs interaction with SETD7. 1 Publication

Organism-specific databases

MalaCardsiNR1H4.
Orphaneti69665. Intrahepatic cholestasis of pregnancy.
PharmGKBiPA31752.

Chemistry

ChEMBLiCHEMBL2047.
DrugBankiDB06777. Chenodeoxycholic acid.
GuidetoPHARMACOLOGYi603.

Polymorphism and mutation databases

BioMutaiNR1H4.
DMDMi46577705.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 486486Bile acid receptorPRO_0000053538Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki132 – 132Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Probable1 Publication
Modified residuei145 – 1451Phosphoserine; by PKC/PRKCA1 Publication
Modified residuei164 – 1641Phosphoserine; by PKC/PRKCA1 Publication
Modified residuei167 – 1671N6-acetyllysine; by EP300
Modified residuei220 – 2201N6-methyllysine; by SETD71 Publication
Modified residuei227 – 2271N6-acetyllysine; by EP300
Cross-linki289 – 289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Probable1 Publication
Modified residuei456 – 4561Phosphothreonine; by PKC/PRKCZ Probable1 Publication

Post-translational modificationi

Acetylated by EP300. Lys-227 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1.1 Publication
Methylation may increase transactivation of target genes.1 Publication
Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.1 Publication
Sumoylated upon ligand binding.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96RI1.
PaxDbiQ96RI1.
PRIDEiQ96RI1.

PTM databases

iPTMnetiQ96RI1.
PhosphoSiteiQ96RI1.

Expressioni

Tissue specificityi

Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximative equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximative equal proportions. Expressed in pancreatic beta cells and macrophages.4 Publications

Gene expression databases

BgeeiQ96RI1.
CleanExiHS_NR1H4.
ExpressionAtlasiQ96RI1. baseline and differential.
GenevisibleiQ96RI1. HS.

Organism-specific databases

HPAiHPA047699.

Interactioni

Subunit structurei

Binds DNA predominantly as a heterodimer with RXRA. After activation by agonist binding interacts with coactivators. Interacts with NCOA1, NCOA2, PPARGC1A, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1 (PubMed:15202934, PubMed:14684751, PubMed:15187081, PubMed:15471871, PubMed:15911693, PubMed:17895379, PubMed:18755856, PubMed:19805516, PubMed:23462506, PubMed:12718892, PubMed:12718893, PubMed:18621523, PubMed:18391212, PubMed:19410460, PubMed:19586769). Interacts with EP300 and SMARCD1 (By similarity). Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP (PubMed:19833092). Interacts with PAGR1 AND NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM) (PubMed:19556342).By similarity17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ESR1P033722EBI-10921781,EBI-78473
NCOA1Q157884EBI-1250177,EBI-455189
PRKDCP785274EBI-9640524,EBI-352053
SETD7Q8WTS65EBI-1250177,EBI-1268586

GO - Molecular functioni

  • ligand-dependent nuclear receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi115296. 25 interactions.
DIPiDIP-39370N.
IntActiQ96RI1. 12 interactions.
STRINGi9606.ENSP00000447149.

Chemistry

BindingDBiQ96RI1.

Structurei

Secondary structure

1
486
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi261 – 27414Combined sources
Helixi281 – 2899Combined sources
Helixi294 – 31724Combined sources
Helixi322 – 3243Combined sources
Helixi327 – 34923Combined sources
Turni354 – 3563Combined sources
Helixi360 – 3678Combined sources
Turni368 – 3703Combined sources
Helixi373 – 38715Combined sources
Turni388 – 3903Combined sources
Helixi393 – 40412Combined sources
Beta strandi407 – 4115Combined sources
Helixi415 – 43622Combined sources
Helixi443 – 46523Combined sources
Beta strandi468 – 4725Combined sources
Helixi477 – 4826Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1OSHX-ray1.80A258-486[»]
1OSKmodel-A258-486[»]
3BEJX-ray1.90A/B249-486[»]
3DCTX-ray2.50A252-486[»]
3DCUX-ray2.95A252-486[»]
3FLIX-ray2.00A258-486[»]
3FXVX-ray2.26A258-486[»]
3GD2X-ray3.20A260-486[»]
3HC5X-ray2.60A257-486[»]
3HC6X-ray3.20A257-486[»]
3L1BX-ray1.90A258-486[»]
3OKHX-ray2.50A258-486[»]
3OKIX-ray2.00A/C258-486[»]
3OLFX-ray1.90A/C258-486[»]
3OMKX-ray1.90A/C258-486[»]
3OMMX-ray2.10A/C258-486[»]
3OOFX-ray2.29A/C258-486[»]
3OOKX-ray2.29A/C258-486[»]
3P88X-ray2.95A258-486[»]
3P89X-ray2.30A258-486[»]
3RUTX-ray3.00A258-486[»]
3RUUX-ray2.50A258-486[»]
3RVFX-ray3.10A257-486[»]
4OIVX-ray1.70A/B258-483[»]
4QE6X-ray1.65A258-486[»]
4QE8X-ray2.62A/B258-486[»]
4WVDX-ray2.90A/B258-468[»]
ProteinModelPortaliQ96RI1.
SMRiQ96RI1. Positions 128-485.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96RI1.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni256 – 474219Ligand-bindingAdd
BLAST
Regioni342 – 3509Agonist bindingBy similarity

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri137 – 15721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri173 – 19725NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00840000129681.
HOVERGENiHBG108655.
InParanoidiQ96RI1.
KOiK08537.
OMAiMKPAKGV.
OrthoDBiEOG7DC25S.
PhylomeDBiQ96RI1.
TreeFamiTF316304.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96RI1-3) [UniParc]FASTAAdd to basket

Also known as: FXRalpha2(+), FXRalpha1, FXRbeta1

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
MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN
60 70 80 90 100
LEVEPYSQYS NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR
110 120 130 140 150
MPAETLYQGE TEVAEMPVTK KPRMGASAGR IKGDELCVVC GDRASGYHYN
160 170 180 190 200
ALTCEGCKGF FRRSITKNAV YKCKNGGNCV MDMYMRRKCQ ECRLRKCKEM
210 220 230 240 250
GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG RDLRQVTSTT
260 270 280 290 300
KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI
310 320 330 340 350
LTEMATNHVQ VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF
360 370 380 390 400
NKKLPSGHSD LLEERIRNSG ISDEYITPMF SFYKSIGELK MTQEEYALLT
410 420 430 440 450
AIVILSPDRQ YIKDREAVEK LQEPLLDVLQ KLCKIHQPEN PQHFACLLGR
460 470 480
LTELRTFNHH HAEMLMSWRV NDHKFTPLLC EIWDVQ
Note: Produced by alternative promoter usage.
Length:486
Mass (Da):55,914
Last modified:April 26, 2004 - v2
Checksum:iC23283576A8CF76B
GO
Isoform 2 (identifier: Q96RI1-4) [UniParc]FASTAAdd to basket

Also known as: FXRalpha2(-), FXRalpha4, FXRbeta2

The sequence of this isoform differs from the canonical sequence as follows:
     207-210: Missing.

Note: Produced by alternative splicing of isoform 1.
Show »
Length:482
Mass (Da):55,462
Checksum:i2B9B563B0999C91D
GO
Isoform 3 (identifier: Q96RI1-1) [UniParc]FASTAAdd to basket

Also known as: FXRalpha1(+), FXRalpha1

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF

Note: Produced by alternative promoter usage.
Show »
Length:476
Mass (Da):54,862
Checksum:i37FB0351FB447544
GO
Isoform 4 (identifier: Q96RI1-2) [UniParc]FASTAAdd to basket

Also known as: FXRalpha1(-), FXRalpha2

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     207-210: Missing.

Note: Produced by alternative splicing of isoform 3.
Show »
Length:472
Mass (Da):54,409
Checksum:i0A53D414B9049C4C
GO
Isoform 5 (identifier: Q96RI1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     159-209: Missing.

Note: Produced by alternative splicing of isoform 3. No experimental confirmation available.
Show »
Length:425
Mass (Da):48,795
Checksum:iF29FB6B5C5FA2257
GO

Sequence cautioni

The sequence BC144183 differs from that shown. Reason: Frameshift at position 156. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti198 – 1981K → R in AAI44185 (PubMed:15489334).Curated
Sequence conflicti217 – 2171C → V in BC144183 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3636MVMQF…MKPAK → MGSKMNLIEHSHLPTTDEFS FSENLF in isoform 3, isoform 4 and isoform 5. 3 PublicationsVSP_010135Add
BLAST
Alternative sequencei159 – 20951Missing in isoform 5. 1 PublicationVSP_044547Add
BLAST
Alternative sequencei207 – 2104Missing in isoform 2 and isoform 4. 2 PublicationsVSP_003665

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68233 mRNA. Translation: AAB08107.1.
AF384555 mRNA. Translation: AAK60271.1.
AF478445 mRNA. Translation: AAM53550.1.
AF478446 mRNA. Translation: AAM53551.1.
AK296612 mRNA. Translation: BAH12398.1.
AC010200 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97639.1.
BC144183 mRNA. No translation available.
BC144184 mRNA. Translation: AAI44185.1.
BC130573 mRNA. Translation: AAI30574.1.
CCDSiCCDS55873.1. [Q96RI1-1]
CCDS55874.1. [Q96RI1-5]
CCDS55875.1. [Q96RI1-4]
CCDS55876.1. [Q96RI1-3]
CCDS9078.1. [Q96RI1-2]
RefSeqiNP_001193906.1. NM_001206977.1. [Q96RI1-1]
NP_001193907.1. NM_001206978.1. [Q96RI1-5]
NP_001193908.1. NM_001206979.1. [Q96RI1-1]
NP_001193921.1. NM_001206992.1. [Q96RI1-4]
NP_001193922.1. NM_001206993.1. [Q96RI1-3]
NP_005114.1. NM_005123.3. [Q96RI1-2]
XP_011537342.1. XM_011539040.1. [Q96RI1-1]
UniGeneiHs.282735.
Hs.732506.

Genome annotation databases

EnsembliENST00000188403; ENSP00000188403; ENSG00000012504. [Q96RI1-4]
ENST00000392986; ENSP00000376712; ENSG00000012504. [Q96RI1-1]
ENST00000548884; ENSP00000448506; ENSG00000012504. [Q96RI1-2]
ENST00000549996; ENSP00000448978; ENSG00000012504. [Q96RI1-5]
ENST00000551379; ENSP00000447149; ENSG00000012504. [Q96RI1-3]
GeneIDi9971.
KEGGihsa:9971.
UCSCiuc001thp.3. human. [Q96RI1-3]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Farnesoid X receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68233 mRNA. Translation: AAB08107.1.
AF384555 mRNA. Translation: AAK60271.1.
AF478445 mRNA. Translation: AAM53550.1.
AF478446 mRNA. Translation: AAM53551.1.
AK296612 mRNA. Translation: BAH12398.1.
AC010200 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97639.1.
BC144183 mRNA. No translation available.
BC144184 mRNA. Translation: AAI44185.1.
BC130573 mRNA. Translation: AAI30574.1.
CCDSiCCDS55873.1. [Q96RI1-1]
CCDS55874.1. [Q96RI1-5]
CCDS55875.1. [Q96RI1-4]
CCDS55876.1. [Q96RI1-3]
CCDS9078.1. [Q96RI1-2]
RefSeqiNP_001193906.1. NM_001206977.1. [Q96RI1-1]
NP_001193907.1. NM_001206978.1. [Q96RI1-5]
NP_001193908.1. NM_001206979.1. [Q96RI1-1]
NP_001193921.1. NM_001206992.1. [Q96RI1-4]
NP_001193922.1. NM_001206993.1. [Q96RI1-3]
NP_005114.1. NM_005123.3. [Q96RI1-2]
XP_011537342.1. XM_011539040.1. [Q96RI1-1]
UniGeneiHs.282735.
Hs.732506.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1OSHX-ray1.80A258-486[»]
1OSKmodel-A258-486[»]
3BEJX-ray1.90A/B249-486[»]
3DCTX-ray2.50A252-486[»]
3DCUX-ray2.95A252-486[»]
3FLIX-ray2.00A258-486[»]
3FXVX-ray2.26A258-486[»]
3GD2X-ray3.20A260-486[»]
3HC5X-ray2.60A257-486[»]
3HC6X-ray3.20A257-486[»]
3L1BX-ray1.90A258-486[»]
3OKHX-ray2.50A258-486[»]
3OKIX-ray2.00A/C258-486[»]
3OLFX-ray1.90A/C258-486[»]
3OMKX-ray1.90A/C258-486[»]
3OMMX-ray2.10A/C258-486[»]
3OOFX-ray2.29A/C258-486[»]
3OOKX-ray2.29A/C258-486[»]
3P88X-ray2.95A258-486[»]
3P89X-ray2.30A258-486[»]
3RUTX-ray3.00A258-486[»]
3RUUX-ray2.50A258-486[»]
3RVFX-ray3.10A257-486[»]
4OIVX-ray1.70A/B258-483[»]
4QE6X-ray1.65A258-486[»]
4QE8X-ray2.62A/B258-486[»]
4WVDX-ray2.90A/B258-468[»]
ProteinModelPortaliQ96RI1.
SMRiQ96RI1. Positions 128-485.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115296. 25 interactions.
DIPiDIP-39370N.
IntActiQ96RI1. 12 interactions.
STRINGi9606.ENSP00000447149.

Chemistry

BindingDBiQ96RI1.
ChEMBLiCHEMBL2047.
DrugBankiDB06777. Chenodeoxycholic acid.
GuidetoPHARMACOLOGYi603.
SwissLipidsiSLP:000001581.

PTM databases

iPTMnetiQ96RI1.
PhosphoSiteiQ96RI1.

Polymorphism and mutation databases

BioMutaiNR1H4.
DMDMi46577705.

Proteomic databases

EPDiQ96RI1.
PaxDbiQ96RI1.
PRIDEiQ96RI1.

Protocols and materials databases

DNASUi9971.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000188403; ENSP00000188403; ENSG00000012504. [Q96RI1-4]
ENST00000392986; ENSP00000376712; ENSG00000012504. [Q96RI1-1]
ENST00000548884; ENSP00000448506; ENSG00000012504. [Q96RI1-2]
ENST00000549996; ENSP00000448978; ENSG00000012504. [Q96RI1-5]
ENST00000551379; ENSP00000447149; ENSG00000012504. [Q96RI1-3]
GeneIDi9971.
KEGGihsa:9971.
UCSCiuc001thp.3. human. [Q96RI1-3]

Organism-specific databases

CTDi9971.
GeneCardsiNR1H4.
HGNCiHGNC:7967. NR1H4.
HPAiHPA047699.
MalaCardsiNR1H4.
MIMi603826. gene.
neXtProtiNX_Q96RI1.
Orphaneti69665. Intrahepatic cholestasis of pregnancy.
PharmGKBiPA31752.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00840000129681.
HOVERGENiHBG108655.
InParanoidiQ96RI1.
KOiK08537.
OMAiMKPAKGV.
OrthoDBiEOG7DC25S.
PhylomeDBiQ96RI1.
TreeFamiTF316304.

Enzyme and pathway databases

ReactomeiR-HSA-159418. Recycling of bile acids and salts.
R-HSA-192105. Synthesis of bile acids and bile salts.
R-HSA-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-HSA-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-211976. Endogenous sterols.
R-HSA-383280. Nuclear Receptor transcription pathway.
SignaLinkiQ96RI1.
SIGNORiQ96RI1.

Miscellaneous databases

EvolutionaryTraceiQ96RI1.
GeneWikiiFarnesoid_X_receptor.
GenomeRNAii9971.
PROiQ96RI1.
SOURCEiSearch...

Gene expression databases

BgeeiQ96RI1.
CleanExiHS_NR1H4.
ExpressionAtlasiQ96RI1. baseline and differential.
GenevisibleiQ96RI1. HS.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The identification of the cDNA coding for HRR-1, a novel human farnesol receptor."
    Papetti M., Wood N., Lohmar P.D., Bowman M.R.
    Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
  2. "Functional analysis of human farnesol receptor (NR1H4) splicing variant."
    Han J.-I., Bok S.-H., Jeong T.-S.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  3. "Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters."
    Huber R.M., Murphy K., Miao B., Link J.R., Cunningham M.R., Rupar M.J., Gunyuzlu P.L., Haws T.F. Jr., Kassam A., Powell F., Hollis G.F., Young P.R., Mukherjee R., Burn T.C.
    Gene 290:35-43(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING (ISOFORMS 3 AND 4).
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Colon.
  5. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
  8. "Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer."
    Grober J., Zaghini I., Fujii H., Jones S.A., Kliewer S.A., Willson T.M., Ono T., Besnard P.
    J. Biol. Chem. 274:29749-29754(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOMEOSTASIS.
  9. Cited for: FUNCTION IN BA HOEMOSTASIS.
  10. Cited for: FUNCTION IN BA HOEMOSTASIS.
  11. "Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids."
    Kast H.R., Nguyen C.M., Sinal C.J., Jones S.A., Laffitte B.A., Reue K., Gonzalez F.J., Willson T.M., Edwards P.A.
    Mol. Endocrinol. 15:1720-1728(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  12. "Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element."
    Claudel T., Sturm E., Duez H., Torra I.P., Sirvent A., Kosykh V., Fruchart J.C., Dallongeville J., Hum D.W., Kuipers F., Staels B.
    J. Clin. Invest. 109:961-971(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  13. "Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis."
    Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F., Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B., Jones S.A.
    Genes Dev. 17:1581-1591(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOMEOSTASIS.
  14. "FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity."
    Barbier O., Torra I.P., Sirvent A., Claudel T., Blanquart C., Duran-Sandoval D., Kuipers F., Kosykh V., Fruchart J.C., Staels B.
    Gastroenterology 124:1926-1940(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOMEOSTASIS.
  15. Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  16. "Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor."
    Anisfeld A.M., Kast-Woelbern H.R., Meyer M.E., Jones S.A., Zhang Y., Williams K.J., Willson T., Edwards P.A.
    J. Biol. Chem. 278:20420-20428(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  17. Cited for: FUNCTION IN BA HOMEOSTASIS.
  18. "Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor."
    Pineda Torra I., Claudel T., Duval C., Kosykh V., Fruchart J.C., Staels B.
    Mol. Endocrinol. 17:259-272(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  19. "The nuclear bile acid receptor FXR is activated by PGC-1alpha in a ligand-dependent manner."
    Kanaya E., Shiraki T., Jingami H.
    Biochem. J. 382:913-921(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PPARGC1A.
  20. "The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion."
    Lew J.L., Zhao A., Yu J., Huang L., De Pedro N., Pelaez F., Wright S.D., Cui J.
    J. Biol. Chem. 279:8856-8861(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA1, LIGAND-BINDUNG.
  21. "Bile acid-induced negative feedback regulation of the human ileal bile acid transporter."
    Neimark E., Chen F., Li X., Shneider B.L.
    Hepatology 40:149-156(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOEMOSTASIS.
  22. "Identification of DRIP205 as a coactivator for the Farnesoid X receptor."
    Pineda Torra I., Freedman L.P., Garabedian M.J.
    J. Biol. Chem. 279:36184-36191(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MED1.
  23. "Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4."
    Hirokane H., Nakahara M., Tachibana S., Shimizu M., Sato R.
    J. Biol. Chem. 279:45685-45692(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  24. "Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1."
    Ananthanarayanan M., Li S., Balasubramaniyan N., Suchy F.J., Walsh M.J.
    J. Biol. Chem. 279:54348-54357(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOMEOSTASIS, INTERACTION WITH CARM1.
  25. "The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes."
    Rizzo G., Renga B., Antonelli E., Passeri D., Pellicciari R., Fiorucci S.
    Mol. Pharmacol. 68:551-558(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRMT1.
  26. "The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes."
    Landrier J.-F., Eloranta J.J., Vavricka S.R., Kullak-Ublick G.A.
    Am. J. Physiol. 290:G476-G485(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOEMOSTASIS.
  27. "Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase."
    Miyata M., Matsuda Y., Tsuchiya H., Kitada H., Akase T., Shimada M., Nagata K., Gonzalez F.J., Yamazoe Y.
    Drug Metab. Pharmacokinet. 21:315-323(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOEMOSTASIS.
  28. Cited for: POSSIBLE INVOLVEMENT IN INTRAHEPATIC CHOLESTASIS OF PREGNANCY.
  29. "Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis."
    Sanyal S., Baavner A., Haroniti A., Nilsson L.M., Lundaasen T., Rehnmark S., Witt M.R., Einarsson C., Talianidis I., Gustafsson J.A., Treuter E.
    Proc. Natl. Acad. Sci. U.S.A. 104:15665-15670(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOEMOSTASIS, INTERACTION WITH GPS2.
  30. "The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor."
    Frankenberg T., Miloh T., Chen F.Y., Ananthanarayanan M., Sun A.Q., Balasubramaniyan N., Arias I., Setchell K.D., Suchy F.J., Shneider B.L.
    Hepatology 48:1896-1905(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, MUTAGENESIS OF THR-456.
  31. "Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans."
    Kovacs P., Kress R., Rocha J., Kurtz U., Miquel J.F., Nervi F., Mendez-Sanchez N., Uribe M., Bock H.H., Schirin-Sokhan R., Stumvoll M., Moessner J., Lammert F., Wittenburg H.
    J. Hepatol. 48:116-124(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN CHOLESTEROL CHOLELITHIASIS.
  32. "Phosphorylation of farnesoid X receptor by protein kinase C promotes its transcriptional activity."
    Gineste R., Sirvent A., Paumelle R., Helleboid S., Aquilina A., Darteil R., Hum D.W., Fruchart J.C., Staels B.
    Mol. Endocrinol. 22:2433-2447(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-145 AND SER-164, INTERACTION WITH PPARGC1A, MUTAGENESIS OF SER-145 AND SER-164.
  33. "Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression."
    Ohno M., Kunimoto M., Nishizuka M., Osada S., Imagawa M.
    Biochem. Biophys. Res. Commun. 390:738-742(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH XRCC5 AND XRCC6.
  34. "Reciprocal regulation of the bile acid-activated receptor FXR and the interferon-gamma-STAT-1 pathway in macrophages."
    Renga B., Migliorati M., Mencarelli A., Fiorucci S.
    Biochim. Biophys. Acta 1792:564-573(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  35. "FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states."
    Kemper J.K., Xiao Z., Ponugoti B., Miao J., Fang S., Kanamaluru D., Tsang S., Wu S.Y., Chiang C.M., Veenstra T.D.
    Cell Metab. 10:392-404(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-167 AND LYS-227 BY EP300.
  36. "The bile acid receptor FXR is a modulator of intestinal innate immunity."
    Vavassori P., Mencarelli A., Renga B., Distrutti E., Fiorucci S.
    J. Immunol. 183:6251-6261(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INTESTINAL INNATE IMMUNITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, SUMOYLATION.
  37. "Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression."
    Song K.H., Li T., Owsley E., Strom S., Chiang J.Y.
    Hepatology 49:297-305(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BA HOMEOSTASIS.
  38. "Functional specificities of Brm and Brg-1 Swi/Snf ATPases in the feedback regulation of hepatic bile acid biosynthesis."
    Miao J., Fang S., Lee J., Comstock C., Knudsen K.E., Kemper J.K.
    Mol. Cell. Biol. 29:6170-6181(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SMARCA4.
  39. "ASCOM controls farnesoid X receptor transactivation through its associated histone H3 lysine 4 methyltransferase activity."
    Kim D.H., Lee J., Lee B., Lee J.W.
    Mol. Endocrinol. 23:1556-1562(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PAGR1 AND NCOA6.
  40. "The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity."
    Popescu I.R., Helleboid-Chapman A., Lucas A., Vandewalle B., Dumont J., Bouchaert E., Derudas B., Kerr-Conte J., Caron S., Pattou F., Staels B.
    FEBS Lett. 584:2845-2851(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN GLUCOSE HOMEOSTASIS, TISSUE SPECIFICITY.
  41. "Deciphering the nuclear bile acid receptor FXR paradigm."
    Modica S., Gadaleta R.M., Moschetta A.
    Nucl. Recept. Signal. 8:E005-E005(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  42. "Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease."
    Gadaleta R.M., van Erpecum K.J., Oldenburg B., Willemsen E.C., Renooij W., Murzilli S., Klomp L.W., Siersema P.D., Schipper M.E., Danese S., Penna G., Laverny G., Adorini L., Moschetta A., van Mil S.W.
    Gut 60:463-472(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INTESTINAL INFLAMMATION.
  43. Cited for: FUNCTION IN LIPID HOMEOSTASIS.
  44. "Anti-inflammatory and metabolic actions of FXR: insights into molecular mechanisms."
    Hollman D.A., Milona A., van Erpecum K.J., van Mil S.W.
    Biochim. Biophys. Acta 1821:1443-1452(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  45. "Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes."
    Balasubramaniyan N., Ananthanarayanan M., Suchy F.J.
    Am. J. Physiol. 302:G937-G947(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: METHYLATION AT LYS-220 BY SETD7.
  46. Cited for: POSSIBLE INVOLVEMENT IN PRIMARY BILIARY CIRRHOSIS.
  47. "Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition."
    Vaquero J., Monte M.J., Dominguez M., Muntane J., Marin J.J.
    Biochem. Pharmacol. 86:926-939(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION.
  48. "SUMOylation of the farnesoid X receptor (FXR) regulates the expression of FXR target genes."
    Balasubramaniyan N., Luo Y., Sun A.Q., Suchy F.J.
    J. Biol. Chem. 288:13850-13862(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-132 AND LYS-289, MUTAGENESIS OF LYS-132; LYS-289 AND GLU-291.
  49. "Identification of functionally relevant lysine residues that modulate human farnesoid X receptor activation."
    Sun A.Q., Luo Y., Backos D.S., Xu S., Balasubramaniyan N., Reigan P., Suchy F.J.
    Mol. Pharmacol. 83:1078-1086(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LYS-132; LYS-167; LYS-220; LYS-227; LYS-353 AND LYS-474, INTERACTION WITH RXRA AND SETD7.
  50. Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 258-476 IN COMPLEX WITH SYNTHETIC AGONIST FEXARAMINE, FUNCTION, INTERACTION WITH NCOA1.
  51. "Structural basis for bile acid binding and activation of the nuclear receptor FXR."
    Mi L.Z., Devarakonda S., Harp J.M., Han Q., Pellicciari R., Willson T.M., Khorasanizadeh S., Rastinejad F.
    Mol. Cell 11:1093-1100(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 241-469 IN COMPLEXES WITH CHENODEOXYCHOLIC ACID ANALOGS AND NCOA2 COACTIVATOR PEPTIDE.
  52. Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 252-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
  53. "Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation."
    Soisson S.M., Parthasarathy G., Adams A.D., Sahoo S., Sitlani A., Sparrow C., Cui J., Becker J.W.
    Proc. Natl. Acad. Sci. U.S.A. 105:5337-5342(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 249-486 IN COMPLEX WITH STEROID ANALOG MFA-1 AND NCOA1 PEPTIDE, INTERACTION WITH NCOA1, DOMAIN.
  54. Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 260-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
  55. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 257-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
  56. "Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR)."
    Flatt B., Martin R., Wang T.L., Mahaney P., Murphy B., Gu X.H., Foster P., Li J., Pircher P., Petrowski M., Schulman I., Westin S., Wrobel J., Yan G., Bischoff E., Daige C., Mohan R.
    J. Med. Chem. 52:904-907(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 258-486 IN COMPLEX WITH SYNTHETIC AGONIST.
  57. "Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: beneficial modulation of lipids in primates."
    Lundquist J.T., Harnish D.C., Kim C.Y., Mehlmann J.F., Unwalla R.J., Phipps K.M., Crawley M.L., Commons T., Green D.M., Xu W., Hum W.T., Eta J.E., Feingold I., Patel V., Evans M.J., Lai K., Borges-Marcucci L., Mahaney P.E., Wrobel J.E.
    J. Med. Chem. 53:1774-1787(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 248-476 IN COMPLEX WITH SYNTHETIC AGONIST.

Entry informationi

Entry nameiNR1H4_HUMAN
AccessioniPrimary (citable) accession number: Q96RI1
Secondary accession number(s): A1L4K5
, B7Z412, B7ZM06, F8VYG8, Q8NFP5, Q8NFP6, Q92943
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: April 26, 2004
Last modified: July 6, 2016
This is version 164 of the entry and version 2 of the sequence. [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

Miscellaneous

Ursodeoxycholic (UDCA), a natural agonist of FXR, is approved to treat primary biliary cirrhosis. However, effects are discussed controversial. UDCA is also used to dissolve (cholesterol) gallstones as alternative to surgery.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.