Product Details

Purity

>85% (SDS-PAGE)

Target Names

Nr1h4

Uniprot No.

Q62735

Alternative Names

Nr1h4; Bar; Fxr; Rip14; Bile acid receptor; Farnesoid X-activated receptor; Farnesol receptor HRR-1; Nuclear receptor subfamily 1 group H member 4; Retinoid X receptor-interacting protein 14; RXR-interacting protein 14

Species

Rattus norvegicus (Rat)

Expression Region

1-469

Target Protein Sequence

MNLIGPSHLQ ATDEFALSEN LFGVLTEHAA GPLGQNLDLE SYSPYNNVQF PQVQPQISSS SYYSNLGFYP QQPEDWYSPG LYELRRMPTE SVYQGETEVS EMPVTKKPRM AASSAGRIKG DELCVVCGDR ASGYHYNALT CEGCKGFFRR SITKNAVYKC KNGGNCVMDM YMRRKCQDCR LRKCREMGML AECLLTEIQC KSKRLRKNVK QHADQTVNED SEGRDLRQVT STTKLCREKT ELTVDQQTLL DYIMDSYSKQ RMPQEITNKI LKEEFSAEEN FLILTEMATS HVQILVEFTK RLPGFQTLDH EDQIALLKGS AVEAMFLRSA EIFNKKLPAG HADLLEERIR KSGISDEYIT PMFSFYKSVG ELKMTQEEYA LLTAIVILSP DRQYIKDREA VEKLQEPLLD VLQKLCKIYQ PENPQHFACL LGRLTELRTF NHHHAEMLMS WRVNDHKFTP LLCEIWDVQ

Protein Length

full length protein

Tag Info

Tag type will be determined during the manufacturing process.

The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.

Form

Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer before Lyophilization

Tris/PBS-based buffer, 6% Trehalose, pH 8.0

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet

Please contact us to get it.

Target Background

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. 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. 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). 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). 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). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression. 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. 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). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). 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. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier. Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. 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. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit proinflammatory (but not antiapoptotic) NF-kappa-B signaling.

Gene References into Functions

expression in intestine decreased during progression of glucose intolerance PMID: 28946907
In summary, the present study provides the first comprehensive analysis of the critical role of the vagus nerve in regulating BA metabolism and signaling pathway. PMID: 29198707
The authors found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals. PMID: 27190252
FXR could be a target molecule for reducing portal hypertension during hepatic fibrosis. PMID: 27896916
Altered mRNA expression of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were significantly restored (p<0.05) by naringin treatment. Naringin treatment also reduced histological alteration induced by APAP in the liver and kidney. Naringin exerts its hepato- and nephroprotective effect via modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression. PMID: 27050864
FXR activation by chenodeoxycholic acid did not reduce body weight, but it lowered the plasma levels of fasting glucose, insulin and triglycerides in the type 2 diabetes mellitus rats. PMID: 26782298
FXR expression was significantly elevated in pulmonary artery hypertension (PAH) and right heart failure (RHF) lungs but reduced in PAH and RHF right ventricular tissues. PMID: 26392308
Confirm the choleretic ability of boldine results from stimulation of the Bsep transcriptional regulator, FXR receptor. PMID: 25771127
Farnesoid X receptor has a role in preventing biliary injuries of liver grafts in a pathway involving cholangiocyte bile acid transport PMID: 24266967
Atherogenic diet-induced accumulation of triglyceride and cholesterol is associated with a substantial decrease in gene expression of the FXR nuclear receptor. FXR gene expression was not altered by the diet in the jejunum. PMID: 23117815
Data suggest that FXR/Nr1h4 in mouse hepatocytes but not in rat or human hepatocytes regulates inflammatory processes through ORM/AGP transcriptional control of ORM/AGP (orosomucoid/alpha1-acid glycoprotein) gene cluster. PMID: 23861371
Downregulation of TBA/FXR expression during biliary obstruction results in damage to intestinal epithelium. PMID: 23410061
FXR activation by a natural, chenodeoxycholic acid (CDCA), and synthetic, GW4064, agonists modulates the expression of genes involved in the lipid beta-oxidation in the cardiomyocytes. PMID: 21924881
FXR, PXR and CAR expression levels are decreased in the liver after intestinal ischemia-reperfusion; interleukin-6 is one of main causes the decreases in expressions of these receptors. PMID: 23331901
The reduction in the bile acid pool size was found to delay the liver regeneration, which may be caused by the down-regulation of FXR and c-Jun expression. PMID: 20155456
Farnesoid X receptor regulates vascular reactivity through nitric oxide mechanism PMID: 23070085
the enhanced enterohepatic flux of bile acids during HF-LC consumption leads to activation of hepatic FXR and FGF19 signaling activity and an increase in FGF21 gene expression and secretion. PMID: 22661717
the regulation of gluconeogenic genes and the gene encoding short heterodimeric partner PMID: 20305288
FXR plays an important role in modulating the metabolism of bile acids. PMID: 18510855
FXR regulates bile acid amidation, a critical component of the enterohepatic circulation of bile acids PMID: 12754200
In vitro, FXR is present in vascular smooth muscle cells. PMID: 14990788
FXR is regulated by glucose likely via the pentose phosphate pathway and is decreased in experimental diabetes. PMID: 15047603
The FXR-SHP regulatory receptor cascade promotes resolution of liver fibrosis PMID: 15521018
farnesoid X receptor regulates carbohydrate metabolism PMID: 15564327
complement C3 expression is regulated by the bile acid receptor FXR PMID: 15590640
activation of FXR may suppress glycolysis and enhance oxidation of fatty acids via inactivation of the pyruvate dehydrogenase complex by increasing PDK4 expression PMID: 15721319
FXR may play a role in endothelial homeostasis and may serve as a novel molecular target for manipulating ET-1 expression in vascular EC. PMID: 16357303
FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells. PMID: 18006431
FXR-mediated regulation of eNOS expression in vascular endothelial cells. PMID: 18006476
FXR is expressed and induces its target gene SHP in VSMCs, and activation of FXR and SHP lead to downregulation of important contributors to vascular inflammation and migration, notably COX-2 and iNOS. PMID: 18029909
The mechanism of cytosol-nuclear transport of small organic molecules, including conjugated bile acids, depend on other mechanisms than simple diffusional exchange. PMID: 18467501
ATP8B1 deficiency predisposes to cholestasis by favoring bile acid-induced injury in the canalicular membrane but does not directly affect FXR expression PMID: 19027009
These results demonstrate that cystathionase is a farnesoid X receptor-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension. PMID: 19418582

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Subcellular Location

Nucleus.

Protein Families

Nuclear hormone receptor family, NR1 subfamily

Database Links

KEGG: rno:60351

STRING: 10116.ENSRNOP00000009910

UniGene: Rn.42943

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Recombinant Rat Bile acid receptor (Nr1h4)

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Target Background

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