ABCB11
ATP-binding cassette, sub-family B member 11 also known as ABCB11 is a protein which in humans is encoded by the ABCB11 gene.[1]
Function
The product of the ABCB11 gene is an ABC transporter named BSEP (Bile Salt Export Pump), or sPgp (sister of P-glycoprotein). This membrane-associated protein is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White).[2]
This protein is a member of the MDR/TAP subfamily. Some members of the MDR/TAP subfamily are involved in multidrug resistance. This particular protein is responsible for the transport of taurocholate and other cholate conjugates from hepatocytes (liver cells) to the bile. In humans, the activity of this transporter is the major determinant of bile formation and bile flow.[3][4][5][6]
Clinical significance
ABCB11 is a gene associated with progressive familial intrahepatic cholestasis type 2 (PFIC2).[1][7][8][9] PFIC2 caused by mutations in the ABCB11 gene increases the risk of hepatocellular carcinoma in early life.[10]
References
- ^ a b Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Németh A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM, Thompson RJ (November 1998). "A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis". Nat. Genet. 20 (3): 233–8. doi:10.1038/3034. PMID 9806540.
- ^ "Entrez Gene: ABCB11". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8647.
- ^ Noé J, Stieger B, Meier PJ (November 2002). "Functional expression of the canalicular bile salt export pump of human liver". Gastroenterology 123 (5): 1659–66. doi:10.1053/gast.2002.36587. PMID 12404240.
- ^ Arrese M, Ananthanarayanan M (November 2004). "The bile salt export pump: molecular properties, function and regulation". Pflugers Arch. 449 (2): 123–31. doi:10.1007/s00424-004-1311-4. PMID 15578267.
- ^ Stieger B, Meier Y, Meier PJ (February 2007). "The bile salt export pump". Pflugers Arch. 453 (5): 611–20. doi:10.1007/s00424-006-0152-8. PMID 17051391.
- ^ Zinchuk V, Okada T, Akimaru K, Seguchi H (March 2002). "Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver". Am J Physiol Gastrointest Liver Physiol. 282 (3): G540–G8. doi:10.1152/ajpgi.00405.2001. PMID 11842005.
- ^ Jansen PL, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ, Koning JH, De Jager-Krikken A, Kuipers F, Stellaard F, Bijleveld CM, Gouw A, Van Goor H, Thompson RJ, Müller M (December 1999). "Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis". Gastroenterology 117 (6): 1370–9. doi:10.1016/S0016-5085(99)70287-8. PMID 10579978.
- ^ van Mil SW, van der Woerd WL, van der Brugge G, Sturm E, Jansen PL, Bull LN, van den Berg IE, Berger R, Houwen RH, Klomp LW (August 2004). "Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11". Gastroenterology 127 (2): 379–84. doi:10.1053/j.gastro.2004.04.065. PMID 15300568.
- ^ Noe J, Kullak-Ublick GA, Jochum W, Stieger B, Kerb R, Haberl M, Müllhaupt B, Meier PJ, Pauli-Magnus C (September 2005). "Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis". J. Hepatol. 43 (3): 536–43. doi:10.1016/j.jhep.2005.05.020. PMID 16039748.
- ^ Knisely AS, Strautnieks SS, Meier Y, Stieger B, Byrne JA, Portmann BC, Bull LN, 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 KM, Whitington PF, Mieli-Vergani G, Thompson RJ (August 2006). "Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency". Hepatology 44 (2): 478–86. doi:10.1002/hep.21287. PMID 16871584.
Further reading
- Guey LT, GarcÃa-Closas M, Murta-Nascimento C, et al. (2010). "Genetic susceptibility to distinct bladder cancer subphenotypes.". Eur. Urol. 57 (2): 283–92. doi:10.1016/j.eururo.2009.08.001. PMID 19692168.
- Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL (2009). "Nuclear factor erythroid 2-related factor 2 is a positive regulator of human bile salt export pump expression.". Hepatology 50 (5): 1588–96. doi:10.1002/hep.23151. PMC 3013376. PMID 19821532. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3013376.
- Rose CS, Grarup N, Krarup NT, et al. (2009). "A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads.". Diabetologia 52 (10): 2122–9. doi:10.1007/s00125-009-1463-z. PMID 19669124.
- Dixon PH, van Mil SW, Chambers J, et al. (2009). "Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy.". Gut 58 (4): 537–44. doi:10.1136/gut.2008.159541. PMID 18987030.
- Acalovschi M, Tirziu S, Chiorean E, et al. (2009). "Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs with gallstones, and controls.". Lipids 44 (6): 521–6. doi:10.1007/s11745-009-3300-z. PMID 19408031.
- Chen HL, Liu YJ, Su YN, et al. (2008). "Diagnosis of BSEP/ABCB11 mutations in Asian patients with cholestasis using denaturing high performance liquid chromatography.". J. Pediatr. 153 (6): 825–32. doi:10.1016/j.jpeds.2008.06.034. PMID 18692205.
- Thompson R, Strautnieks S (2001). "BSEP: function and role in progressive familial intrahepatic cholestasis.". Semin. Liver Dis. 21 (4): 545–50. doi:10.1055/s-2001-19038. PMID 11745042.
- Kim SR, Saito Y, Itoda M, et al. (2009). "Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population.". Drug Metab. Pharmacokinet. 24 (3): 277–81. doi:10.2133/dmpk.24.277. PMID 19571440.
- Saito A, Kawamoto M, Kamatani N (2009). "Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects.". J. Hum. Genet. 54 (6): 317–23. doi:10.1038/jhg.2009.31. PMID 19343046.
- Hosgood HD, Menashe I, He X, et al. (2009). "PTEN identified as important risk factor of chronic obstructive pulmonary disease.". Respir Med 103 (12): 1866–70. doi:10.1016/j.rmed.2009.06.016. PMC 2783799. PMID 19625176. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2783799.
- Hosgood HD, Menashe I, Shen M, et al. (2008). "Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.". Carcinogenesis 29 (10): 1938–43. doi:10.1093/carcin/bgn178. PMC 2722857. PMID 18676680. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2722857.
- Ross CJ, Katzov-Eckert H, Dubé MP, et al. (2009). "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy.". Nat. Genet. 41 (12): 1345–9. doi:10.1038/ng.478. PMID 19898482.
- Lu Y, Dollé ME, Imholz S, et al. (2008). "Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.". J. Lipid Res. 49 (12): 2582–9. doi:10.1194/jlr.M800232-JLR200. PMID 18660489.
- Byrne JA, Strautnieks SS, Ihrke G, et al. (2009). "Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing.". Hepatology 49 (2): 553–67. doi:10.1002/hep.22683. PMID 19101985.
- Ho RH, Leake BF, Kilkenny DM, et al. (2010). "Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability.". Pharmacogenet. Genomics 20 (1): 45–57. doi:10.1097/FPC.0b013e3283349eb0. PMC 2883163. PMID 20010382. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2883163.
- Takeuchi F, Katsuya T, Chakrewarthy S, et al. (2010). "Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.". Diabetologia 53 (2): 299–308. doi:10.1007/s00125-009-1595-1. PMID 19937311.
- Ohno M, Kunimoto M, Nishizuka M, et al. (2009). "Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression.". Biochem. Biophys. Res. Commun. 390 (3): 738–42. doi:10.1016/j.bbrc.2009.10.040. PMID 19833092.
- Andreotti G, Menashe I, Chen J, et al. (2009). "Genetic determinants of serum lipid levels in Chinese subjects: a population-based study in Shanghai, China.". Eur. J. Epidemiol. 24 (12): 763–74. doi:10.1007/s10654-009-9402-3. PMC 2885778. PMID 19888660. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2885778.
- Sabatti C, Service SK, Hartikainen AL, et al. (2009). "Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.". Nat. Genet. 41 (1): 35–46. doi:10.1038/ng.271. PMC 2687077. PMID 19060910. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2687077.
- Kosters A, Karpen SJ (2008). "Bile acid transporters in health and disease.". Xenobiotica 38 (7-8): 1043–71. doi:10.1080/00498250802040584. PMC 2823065. PMID 18668439. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2823065.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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see also ABC transporter disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr
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