ABCB11 Membrane Protein Introduction

Introduction of ABCB11

ABCB11 encoded by ABCB11 gene, also known as BSEP, is a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intracellular membranes. There are seven subfamilies in ABC superfamily named as ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White, respectively. BSEP possesses 12 transmembrane domains and belongs to MDR/TAP subfamily. It is most expressed in the canalicular membrane of hepatocytes.

Function of ABCB11 Membrane Protein

ABCB11 is an ATP-dependent transporter of conjugated bile acids such as taurine-amidated and acyl-glucuronides. It is also reported as a high-affinity bile salt transporter such as glycochenodeoxycholate, glycocholate and taurochenodeoxycholate. ABCB11 is a major regulator of bile formation and bile flow, which plays an essential role in maintaining normal liver functions. The lacking ABCB11 function can decrease biliary bile salt secretion and bile flow, as well as the accumulation of the bile salts in hepatocytes, resulting in hepatotoxicity or cholestasis in humans. It has been revealed that mutations of ABCB11 have an association with the progression of cholestatic liver disease such as progressive familial intrahepatic cholestasis type 2 (PFIC2). And PFIC2 may increase the susceptibility of hepatocellular carcinoma in early life. Moreover, the variants in ABCB11 have been also revealed a role in the progression of anti-tuberculosis drug-induced cholestatic liver injury. Besides, ABCB11 also affect drug absorption by regulating the production of bile salt. It can bind to biliary cholesterol and phospholipids forming the micelles which promote drugs solubilization and absorption by the intestine.

Fig.1 Hypothetical mechanism of canalicular lipid excretion. (Elferink, 2007)

Application of ABCB11 Membrane Protein in Literature

1. Sharma A., et al. Spectrum of genomic variations in Indian patients with progressive familial intrahepatic cholestasis. BMC Gastroenterol. 2018, 18(1): 107. PubMed ID: 29973134
   
   

   The study shows nine major genomic variations in ATP8B1, ABCB11 and ABCB4 genes associated with one-third of Indian children with progressive familial intrahepatic cholestasis (PFIC).

2. Imagawa K., et al. Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis. Journal of Human Genetics. 2018, 63(5): 569-577. PubMed ID: 29507376
   
   

   The study indicates that the variant c.386G>A (p.C129Y) in ABCB11 is associated with progression of familial intrahepatic cholestasis type 2 with an impaired biliary excretion from hepatocytes and the inexistence of canalicular BSEP expression in liver histological assessments.

3. Besheer T., et al. Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels. Turkish Journal of Gastroenterology. 2018, 29(3): 299-307. PubMed ID: 29755014
   
   

   The study reveals that the Egyptian patients with chronic hepatitis C genotype 4 who carry CC genotype of ABCB11 SNP 1331T > C and present high plasma bile acid levels are linked to advanced hepatic fibrosis.

4. Wang N.L., et al. Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low γ-glutamyltransferase. Hepatology Research. 2018, 48(7): 574-584. PubMed ID: 29316097
   
   

   The study identifies five rare synonymous or intronic variants in ABCB11 heterozygotes, which are involved in the progression of intrahepatic cholestasis with low γ-glutamyltransferase.

5. Dixon P.H., et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Sci Rep. 2017, 7(1): 11823. PubMed ID: 28924228
   
   

   The study expands known variants in ABCB4 and ABCB11 and identifies the roles in intrahepatic cholestasis of pregnancy (ICP) for mutations in ATP8B1 and ABCC2.

ABCB11 Preparation Options

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Reference

1. Elferink R P and Paulusma C C. (2007). Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflügers Archiv: European Journal of Physiology. 453(5): 601-610.

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