Stable Identifier
Reaction [binding]
Homo sapiens
FXR:bile acids binds RXRA and NCOA1,2
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The nuclear orphan protein bile acid receptor aka farnesoid X-activated receptor (NR1H4 aka FXR) can be activated by bile acids and their salts, its physiological ligands. Bile acids tested to activate NR1H4 are chenodeoxycholic acid (CDCA), lithocholic acid (LCHA) and deoxycholic acid (DCA) (Parks et al. 1999, Makishima et al. 1999). Once bound to its ligand, activated NR1H4 binds to retinoic acid receptor RXR-alpha (RXRA) and either nuclear receptor coactivator 1 or 2 (NCOA1 or 2) to function as a ligand-activated transcription factor. This complex repressed transcription of the CYP7A1 gene (encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis) (Holt et al. 2003) and activated the SLC10A2 and 6 genes (encoding Ileal sodium/bile acid cotransporters; both bile acid transporters) (Plass et al. 2002, Ananthanarayanan et al. 2001). Thus, NR1H4 is one of the most important regulators of bile acid metabolism, regulating bile acid synthesis, conjugation, secretion and uptake (Lee et al. 2006, Houten et al. 2006).
Literature References
PubMed ID Title Journal Year
10334992 Identification of a nuclear receptor for bile acids

Hull, MV, Lustig, KD, Learned, RM, Okamoto, AY, Makishima, M, Repa, JJ, Mangelsdorf, DJ, Luk, A, Shan, B, Tu, H

Science 1999
11387316 Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor

Suchy, FJ, Balasubramanian, N, Mangelsdorf, DJ, Makishima, M, Ananthanarayanan, M

J. Biol. Chem. 2001
16541101 Endocrine functions of bile acids

Watanabe, M, Houten, SM, Auwerx, J

EMBO J. 2006
12815072 Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis

Goodwin, B, Bisi, J, Holt, JA, Jones, SA, Kliewer, SA, Wang, DY, Luo, G, McNeill, YY, Kozarsky, KF, Billin, AN, Mansfield, TA, Donahee, M

Genes Dev. 2003
10334993 Bile acids: natural ligands for an orphan nuclear receptor

Chandra, G, Willson, TM, Bledsoe, RK, Moore, DD, Kliewer, SA, Consler, TG, Lehmann, JM, Blanchard, SG, Zavacki, AM, Parks, DJ, Stimmel, JB

Science 1999
16908160 FXR, a multipurpose nuclear receptor

Zhang, Y, Hubbert, ML, Lee, H, Edwards, PA, Lee, FY

Trends Biochem. Sci. 2006
11870371 Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump

Mol, O, Plass, JR, Jansen, PL, Faber, KN, Geuken, M, Müller, M, Heegsma, J

Hepatology 2002
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