Farnesoid X receptor


Farnesoid X receptor
Nuclear receptor subfamily 1, group H, member 4

PDB rendering based on 1osh.
Identifiers
Symbols NR1H4; BAR; FXR; HRR-1; HRR1; MGC163445; RIP14
External IDs OMIM603826 MGI1352464 HomoloGene3760 GeneCards: NR1H4 Gene
RNA expression pattern
PBB GE NR1H4 206340 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 9971 20186
Ensembl ENSG00000012504 ENSMUSG00000047638
UniProt Q96RI1 Q60641
RefSeq (mRNA) NM_001206977.1 NM_009108
RefSeq (protein) NP_001193906.1 NP_033134
Location (UCSC) Chr 12:
100.87 – 100.96 Mb
Chr 10:
88.92 – 89 Mb
PubMed search [1] [2]

The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a nuclear receptor that is encoded by the NR1H4 gene in humans.[1][2]

Contents

Function

FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes.[2]

One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high.

Interactions

Farnesoid X receptor has been shown to interact with Peroxisome proliferator-activated receptor gamma coactivator 1-alpha[3] and Retinoid X receptor alpha.[4]

References

  1. ^ "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9971. 
  2. ^ a b Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C (June 1995). "Identification of a nuclear receptor that is activated by farnesol metabolites". Cell 81 (5): 687–93. doi:10.1016/0092-8674(95)90530-8. PMID 7774010. 
  3. ^ Zhang, Yanqiao; Castellani Lawrence W, Sinal Christopher J, Gonzalez Frank J, Edwards Peter A (Jan. 2004). "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. (United States) 18 (2): 157–69. doi:10.1101/gad.1138104. ISSN 0890-9369. PMC 324422. PMID 14729567. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=324422. 
  4. ^ Seol, W; Choi H S, Moore D D (Jan. 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Mol. Endocrinol. (UNITED STATES) 9 (1): 72–85. doi:10.1210/me.9.1.72. ISSN 0888-8809. PMID 7760852. 

Further reading

External links


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