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Gene Review

ABCB11  -  ATP-binding cassette, sub-family B...

Homo sapiens

Synonyms: ABC16, ATP-binding cassette sub-family B member 11, BRIC2, BSEP, Bile salt export pump, ...
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Disease relevance of ABCB11


Psychiatry related information on ABCB11


High impact information on ABCB11

  • A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q [9].
  • The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane [9].
  • Five mutations, G238V, E297G, G982R, R1153C, and R1268Q, prevented the protein from trafficking to the apical membrane, and E297G, G982R, R1153C, and R1268Q also abolished taurocholate transport activity, possibly by causing Bsep to misfold [10].
  • The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II [10].
  • To evaluate these mechanisms, we introduced seven PFIC II-associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively [10].

Chemical compound and disease context of ABCB11


Biological context of ABCB11

  • An ABCB11 promoter haplotype was associated with significant decrease of activity compared with wild type [15].
  • All coding exons, 5 of 6 noncoding exons, 50 to 300 base pairs of the flanking intronic regions, and 2.5 to 2.8 kilobase pairs of the promoter regions of ABCB4 and ABCB11 were sequenced in 159 and 196 DNA samples of Caucasian, African-American, Japanese, and Korean origin [15].
  • The authors have recently developed in vitro high-speed screening and quantitative structure-activity relationship analysis methods to investigate the interaction of ABCB11 with a variety of compounds [16].
  • Whereas the downregulation of the unidirectional sinusoidal uptake system NTCP protects the hepatocyte from further intracellular accumulation of bile salts, the relative preservation of canalicular BSEP expression serves to uphold bile salt secretion, even in complete biliary obstruction [17].
  • Our data further support an involvement of MDR3 genetic variation in the pathogenesis of ICP, whereas analysis of BSEP sequence variation indicates that this gene is probably less important for the development of pregnancy-associated cholestasis [18].

Anatomical context of ABCB11

  • Under physiological conditions, the sinusoidal ABCC4 may compete with canalicular ABCB11 for bile acids and thereby play a key role in determining the hepatocyte concentration of bile acids [19].
  • After diffusion (bound by intracellular bile salt-binding proteins) to the canalicular membrane, monoanionic bile salts are secreted into bile canaliculi by the bile salt export pump Bsep (rodents) or BSEP (humans) [20].
  • Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs [21].
  • Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents [22].
  • Spgp is a Mr approximately 170,000 glycosylated plasma membrane protein localized to the canalicular surface of hepatocytes in the rat liver [23].

Associations of ABCB11 with chemical compounds


Physical interactions of ABCB11

  • The sister gene of P-glycoprotein (Spgp) is a liver-specific ATP-binding cassette protein highly related to the P-glycoprotein (Pgp) family (S. Childs et al, Cancer Res., 55: 2029-2034, 1995) [23].

Regulatory relationships of ABCB11


Other interactions of ABCB11

  • In conclusion, PFIC-2 may be reliably diagnosed by immunofluorescence, whereas the diagnosis of PFIC-3 requires gene-sequencing [27].
  • In contrast, MRP2 and BSEP mRNA levels were not affected under these conditions [28].
  • Because fluorescent substrates allow the development of a high-throughput screening method, we examined the transport by NTCP and BSEP of fluorescent bile acids as well as taurocholate [21].
  • Bile acid transporters, i.e., bile salt export pump and Na(+)-taurocholate cotransporting polypeptide, and the sinusoidal transporter, OAT2, were down-regulated by all the tested chemicals [29].
  • It has been reported that bosentan, an endothelin receptor antagonist, inhibits Bsep, which may lead to cholestatic liver injury due to the intracellular accumulation of bile salts, while increasing bile salt-independent bile flow [30].

Analytical, diagnostic and therapeutic context of ABCB11


  1. BSEP: function and role in progressive familial intrahepatic cholestasis. Thompson, R., Strautnieks, S. Semin. Liver Dis. (2001) [Pubmed]
  2. Enterohepatic bile salt transporters in normal physiology and liver disease. Kullak-Ublick, G.A., Stieger, B., Meier, P.J. Gastroenterology (2004) [Pubmed]
  3. BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis. Pauli-Magnus, C., Kerb, R., Fattinger, K., Lang, T., Anwald, B., Kullak-Ublick, G.A., Beuers, U., Meier, P.J. Hepatology (2004) [Pubmed]
  4. Hepatic transport of bile salts. Kullak-Ublick, G.A., Stieger, B., Hagenbuch, B., Meier, P.J. Semin. Liver Dis. (2000) [Pubmed]
  5. Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Lam, P., Wang, R., Ling, V. Biochemistry (2005) [Pubmed]
  6. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Lang, C., Meier, Y., Stieger, B., Beuers, U., Lang, T., Kerb, R., Kullak-Ublick, G.A., Meier, P.J., Pauli-Magnus, C. Pharmacogenet. Genomics (2007) [Pubmed]
  7. Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy. Eloranta, M.L., Häkli, T., Hiltunen, M., Helisalmi, S., Punnonen, K., Heinonen, S. Scand. J. Gastroenterol. (2003) [Pubmed]
  8. Competencies and concerns in end-of-life care for medical students and residents. Jubelirer, S.J., Welch, C., Babar, Z., Emmett, M. The West Virginia medical journal. (2001) [Pubmed]
  9. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Strautnieks, S.S., Bull, L.N., Knisely, A.S., Kocoshis, S.A., Dahl, N., Arnell, H., Sokal, E., Dahan, K., Childs, S., Ling, V., Tanner, M.S., Kagalwalla, A.F., Németh, A., Pawlowska, J., Baker, A., Mieli-Vergani, G., Freimer, N.B., Gardiner, R.M., Thompson, R.J. Nat. Genet. (1998) [Pubmed]
  10. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. Wang, L., Soroka, C.J., Boyer, J.L. J. Clin. Invest. (2002) [Pubmed]
  11. Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. Yu, J., Lo, J.L., Huang, L., Zhao, A., Metzger, E., Adams, A., Meinke, P.T., Wright, S.D., Cui, J. J. Biol. Chem. (2002) [Pubmed]
  12. The role of the enterohepatic circulation of bile salts and nuclear hormone receptors in the regulation of cholesterol homeostasis: Bile salts as ligands for nuclear hormone receptors. Redinger, R.N. Can. J. Gastroenterol. (2003) [Pubmed]
  13. Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. Vallejo, M., Briz, O., Serrano, M.A., Monte, M.J., Marin, J.J. J. Hepatol. (2006) [Pubmed]
  14. Metabolic and non-metabolic factors determining troglitazone hepatotoxicity: a review. Masubuchi, Y. Drug Metab. Pharmacokinet. (2006) [Pubmed]
  15. Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11). Lang, T., Haberl, M., Jung, D., Drescher, A., Schlagenhaufer, R., Keil, A., Mornhinweg, E., Stieger, B., Kullak-Ublick, G.A., Kerb, R. Drug Metab. Dispos. (2006) [Pubmed]
  16. Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump. Sakurai, A., Kurata, A., Onishi, Y., Hirano, H., Ishikawa, T. Expert opinion on drug safety (2007) [Pubmed]
  17. Hepatobiliary transport. Kullak-Ublick, G.A., Beuers, U., Paumgartner, G. J. Hepatol. (2000) [Pubmed]
  18. Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pauli-Magnus, C., Lang, T., Meier, Y., Zodan-Marin, T., Jung, D., Breymann, C., Zimmermann, R., Kenngott, S., Beuers, U., Reichel, C., Kerb, R., Penger, A., Meier, P.J., Kullak-Ublick, G.A. Pharmacogenetics (2004) [Pubmed]
  19. Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione. Rius, M., Hummel-Eisenbeiss, J., Hofmann, A.F., Keppler, D. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  20. Bile salt transporters. Meier, P.J., Stieger, B. Annu. Rev. Physiol. (2002) [Pubmed]
  21. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Mita, S., Suzuki, H., Akita, H., Hayashi, H., Onuki, R., Hofmann, A.F., Sugiyama, Y. Drug Metab. Dispos. (2006) [Pubmed]
  22. Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Knisely, A.S., Strautnieks, S.S., Meier, Y., Stieger, B., Byrne, J.A., Portmann, B.C., Bull, L.N., Pawlikowska, L., Bilezikçi, B., Ozçay, F., László, A., Tiszlavicz, L., Moore, L., Raftos, J., Arnell, H., Fischler, B., Németh, A., Papadogiannakis, N., Cielecka-Kuszyk, J., Jankowska, I., Pawłowska, J., Melín-Aldana, H., Emerick, K.M., Whitington, P.F., Mieli-Vergani, G., Thompson, R.J. Hepatology (2006) [Pubmed]
  23. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Childs, S., Yeh, R.L., Hui, D., Ling, V. Cancer Res. (1998) [Pubmed]
  24. Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. Hirano, M., Maeda, K., Hayashi, H., Kusuhara, H., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  25. Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump. Plass, J.R., Mol, O., Heegsma, J., Geuken, M., Faber, K.N., Jansen, P.L., Müller, M. Hepatology (2002) [Pubmed]
  26. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Owsley, E., Chiang, J.Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  27. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Keitel, V., Burdelski, M., Warskulat, U., Kühlkamp, T., Keppler, D., Häussinger, D., Kubitz, R. Hepatology (2005) [Pubmed]
  28. LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. Elferink, M.G., Olinga, P., Draaisma, A.L., Merema, M.T., Faber, K.N., Slooff, M.J., Meijer, D.K., Groothuis, G.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  29. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Jigorel, E., Le Vee, M., Boursier-Neyret, C., Parmentier, Y., Fardel, O. Drug Metab. Dispos. (2006) [Pubmed]
  30. Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Mano, Y., Usui, T., Kamimura, H. Biopharmaceutics & drug disposition (2007) [Pubmed]
  31. Expression in Human Trophoblast and Choriocarcinoma Cell Lines, BeWo, Jeg-3 and JAr of Genes Involved in the Hepatobiliary-like Excretory Function of the Placenta. Serrano, M.A., Macias, R.I., Briz, O., Monte, M.J., Blazquez, A.G., Williamson, C., Kubitz, R., Marin, J.J. Placenta (2007) [Pubmed]
  32. Hepatobiliary membrane transporters involving in the formation of cholesterol calculus. Kong, F.M., Sui, C.Y., Li, Y.J., Guo, K.J., Guo, R.X. HBPD INT (2006) [Pubmed]
  33. Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hayashi, H., Takada, T., Suzuki, H., Akita, H., Sugiyama, Y. Hepatology (2005) [Pubmed]
  34. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. Gerloff, T., Stieger, B., Hagenbuch, B., Madon, J., Landmann, L., Roth, J., Hofmann, A.F., Meier, P.J. J. Biol. Chem. (1998) [Pubmed]
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