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PsychedeliaDokholyan Laboratory
TargetOther named receptors

Bile acid receptor

A named receptor outside the families above. The catch-all is explicit rather than silent: these are receptors, but they are not grouped.

Measurements
4
Compounds
1
Binding constants
0
Median pX
—

I · Identity

What this target is

Its function as UniProt states it, where in a cell the protein is found, and which cell types and tissues transcribe its gene.

Protein

NR1H4_HUMANNR1H4Homo sapiens

Bile acid receptor

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 response10334992,10334993,21383957,22820415. 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)12754200,15471871,17895379. 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)10514450,15239098,16269519. In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression12815072,19085950. 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 RXRA12806625,16946559. 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 assembly12554753,12660231,15337761. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance)11579204. Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element11927623,21804189. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase)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 resistance20447400. 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 cells21242261. 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 NOS219864602. 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)
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
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
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
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

Quoted from UniProt’s FUNCTION annotation for Q96RI1 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

PartnerCombinedExperimentDatabaseText mining
RXRA0.9990.9730.5000.987
NCOA10.9970.9900.5000.451
GPBAR10.9910.0000.0000.991
XPR10.9900.0000.0000.990
CYP7A10.9860.0560.4000.975
NR0B20.9860.0000.0000.981
NCOR10.9830.9350.5000.535
PPARGC1A0.9830.9360.0000.744
NCOA20.9810.9480.5000.344
ABCB110.9640.2920.0000.944

Where it sits in the cell

  • Nucleoplasm
  • Nuclear speckles
  • Primary cilium tipadditional
  • Cytosoladditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Nucleus

Expression by cell type

Single cell type RNA, the 12 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Enterocytes673.5 nCPM
  • Hepatocytes255.6 nCPM
  • Cholangiocytes212.2 nCPM
  • Adrenal cortex cells212.1 nCPM
  • Proximal tubule cells174.9 nCPM
  • Hepatic stellate cells154.9 nCPM
  • Oocytes138.2 nCPM
  • Enteric transient amplifying cells137.8 nCPM
  • Urothelial cells87 nCPM
  • Loop of henle epithelial cells82.8 nCPM
  • Renal collecting duct principal cells82.3 nCPM
  • Paneth cells77.3 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

  • liver112.7 nTPM
  • intestine36.8 nTPM

II · Anatomy

Where the gene is transcribed

The same two atlases the compound plates use, asked about this gene alone. Brain on the left, peripheral and autonomic tissues on the right.

Brain

cerebral cortex — 0.1 nTPM, from NR1H4cerebellum — no resolved target expressed herehippocampal formation — 0.1 nTPM, from NR1H4amygdala — no resolved target expressed herehypothalamus — 0.1 nTPM, from NR1H4thalamus — no resolved target expressed herebasal ganglia — no resolved target expressed heremedulla oblongata — no resolved target expressed here

basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.

Measured but not drawn — this anatomogram has no outline for them: pituitary gland 1.3, retina 0.2.

Body

heart — 0.3 nTPM, from NR1H4smooth muscle — 0.7 nTPM, from NR1H4lung — 0.3 nTPM, from NR1H4liver — 112.7 nTPM, from NR1H4kidney — 26.3 nTPM, from NR1H4stomach — 0.5 nTPM, from NR1H4duodenum — 27.8 nTPM, from NR1H4small intestine — 36.8 nTPM, from NR1H4colon — 7.7 nTPM, from NR1H4adrenal gland — 20.9 nTPM, from NR1H4thyroid gland — 0.2 nTPM, from NR1H4pancreas — 2.9 nTPM, from NR1H4urinary bladder — 6.1 nTPM, from NR1H4skeletal muscle — 0.3 nTPM, from NR1H4spleen — 0.4 nTPM, from NR1H4salivary gland — 0.3 nTPM, from NR1H4
0113 nTPM

Square-root ramp · shared scale across both plates

Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of NR1H4 transcript above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.

Brain · 5

  • pituitary gland1.3 nTPM
  • retina0.2 nTPM
  • cerebral cortex0.1 nTPM
  • hippocampal formation0.1 nTPM
  • hypothalamus0.1 nTPM

Peripheral and autonomic · 16

  • liver112.7 nTPM
  • small intestine36.8 nTPM
  • duodenum27.8 nTPM
  • kidney26.3 nTPM
  • adrenal gland20.9 nTPM
  • colon7.7 nTPM
  • urinary bladder6.1 nTPM
  • pancreas2.9 nTPM
  • smooth muscle0.7 nTPM
  • stomach 10.5 nTPM
  • spleen0.4 nTPM
  • heart muscle0.3 nTPM
  • lung0.3 nTPM
  • skeletal muscle0.3 nTPM
  • salivary gland0.3 nTPM
  • thyroid gland0.2 nTPM

Transcript is not protein. These are RNA levels for NR1H4, shaded on √nTPM so that a three-order range stays legible — on a linear ramp every region but the strongest would read as blank, which looks like absence rather than less. A region carrying no shading is one the atlas reports no consensus value for, not one where the gene is silent. And a gene being transcribed somewhere is not evidence that any compound reaches it. Human Protein Atlas, RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset.

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Functional readouts 4

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

TargetClassTypeValue (nM)pXOrganismAssay
Bile acid receptorOther named receptorsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291840
Bile acid receptorOther named receptorsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291842
Bile acid receptorOther named receptorsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291841
Bile acid receptorOther named receptorsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291843
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