Mouse Anti-NR1H4 Recombinant Antibody (CBXF-1825) (CBMAB-F3360-CQ)

Mouse

Human

CBXF-1825

IgG

WB, IP, IF, ELISA

Human

IgG

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

nuclear receptor subfamily 1, group H, member 4

This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described.

Nuclear Receptor Subfamily 1 Group H Member 4; Retinoid X Receptor-Interacting Protein 14; Farnesoid X-Activated Receptor; RXR-Interacting Protein 14; Farnesol Receptor HRR-1; RIP14; HRR1; BAR;

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: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 an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).
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.
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.
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.
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.

Bile acid metabolic processIEA:Ensembl
Bile acid signaling pathwayISS:BHF-UCL
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell-cell junction assemblyIEA:Ensembl
Cellular glucose homeostasisIEA:Ensembl
Cellular response to bile acidManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to fatty acidManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to lipopolysaccharideIEA:Ensembl
Cellular response to organonitrogen compoundBy SimilarityISS:BHF-UCL
Cellular triglyceride homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Cholesterol homeostasisIEA:Ensembl
Defense response to bacteriumIEA:Ensembl
Fatty acid homeostasisIEA:Ensembl
Histone H3-R17 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Inflammatory responseIEA:UniProtKB-KW
Innate immune responseIEA:UniProtKB-KW
Intracellular bile acid receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular receptor signaling pathwayISS:BHF-UCL
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of inflammatory responseManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of interferon-gamma productionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of interleukin-1 productionIEA:Ensembl
Negative regulation of interleukin-2 productionIEA:Ensembl
Negative regulation of interleukin-6 productionIEA:Ensembl
Negative regulation of monocyte chemotactic protein-1 productionIEA:Ensembl
Negative regulation of NF-kappaB transcription factor activityIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIBy SimilarityISS:BHF-UCL
Negative regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathwayIEA:Ensembl
Negative regulation of very-low-density lipoprotein particle remodelingManual Assertion Based On ExperimentIDA:MGI
Nitrogen catabolite activation of transcription from RNA polymerase II promoter1 PublicationIC:BHF-UCL
Notch signaling pathwayIEA:Ensembl
Positive regulation of adipose tissue developmentIEA:Ensembl
Positive regulation of ammonia assimilation cycleIEA:Ensembl
Positive regulation of glutamate metabolic processBy SimilarityISS:BHF-UCL
Positive regulation of insulin receptor signaling pathwayIEA:Ensembl
Positive regulation of insulin secretion involved in cellular response to glucose stimulusIEA:Ensembl
Positive regulation of interleukin-17 productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphatidic acid biosynthetic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:MGI
Regulation of bile acid biosynthetic processManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of cholesterol metabolic processManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of insulin secretion involved in cellular response to glucose stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of low-density lipoprotein particle clearanceManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription, DNA-templatedIMP:UniProtKB
Regulation of urea metabolic processBy SimilarityISS:BHF-UCL
Toll-like receptor 4 signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Toll-like receptor 9 signaling pathwayIEA:Ensembl

Nucleus

Cholestasis, progressive familial intrahepatic, 5 (PFIC5):
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.

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.
Methylation may increase transactivation of target genes.
Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.
Sumoylated upon ligand binding.