ABCB11

About 200 missense mutations in ABCB11 have been reported.

The frequencies of ABCB11 mutations differ between Asian and European populations. ABCB11 mutation c.386G>A (p.C129Y) that is most frequently reported in Japan.

No, The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings.

The common variant p.Val444Ala in ABCB11 confers increased risk of drug-induced liver injury and intrahepatic cholestasis of pregnancy (ICP).

Bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding cassette transporters, is localized on the canalicular membrane of hepatocytes and mediates the efficient biliary excretion of bile acid.

The major PFIC genes are now described. ATP8B1 encodes FIC1, ABCB11 encodes BSEP, ABCB4 encodes MDR3, TJP2 encodes TJP2, NR1H4 encodes FXR, and MYO5B encodes MYO5B.

Yes, there many inhibitors could inhibit ABCB11. For example, miR-199a-5p would target the 3'-untranslated region (3'-UTR) of ABCB11/Abcb11 mRNA, and inhibits the expression of ABCB11 in obstructive cholestasis

The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype. Patients should be managed in individualized maner.

You could find the result in the Cell Research, https://www.nature.com/articles/s41422-020-0302-0

Some studies show that although an impact of rare variants on BSEP and MDR3 function cannot be ruled out, the data do not support a strong role of BSEP and MDR3 genetic variations in the pathogenesis of PBC and PSC.

ABCB11, more commonly referred to as BSEP (Bile Salt Export Pump) is a uni-directional, ATP-dependent efflux transporter that plays an important role in the elimination of bile salts from the hepatocyte into the bile canaliculi for export into the gastrointestinal tract (GIT).

Homology modelling is useful for you, but you should have a structure of the wild-type protein first.

You can find the cell line in ATCC. Or contact us directly for more information.

Rifampicin and glibenclamide inhibit bile salt transport by ABCB11.

ABCB11 belongs to the B subfamily of ABC transporters. It shows high sequence and structural homology to the multidrug transporter P-glycoprotein (P-gp,MDR1,ABCB1); thus, BSEP was originally named sister of P-gp or Spgp.

The substrate with the highest affinity for human BSEP is taurocholic acid (TC), and the substrate with the highest affinity for mouse BSEP is taurochenodeoxycholic acid (TCDC).

When activated by bile salts, FXR forms a heterodimer with the retinoid X receptor (RXR). The FXR–RXR complex enhances transcription from the ABCB11 promoter.

Similar to P-glycoprotein, BSEP possesses a canonical ABC transporter membrane topology, having a domain order of TMD1-NBD1-TMD2-NBD2, as well as containing a large, heavily glycosylated extracellular loop in the first TMD, between TMH1 and TMH2.

It mainly transports primary conjugated bile acids, including glycocholic acid(GC), taurocholic acid(TC), glycochenodeoxycholic acid(GCDC), and taurochenodeoxycholic acid(TCDC).

Drugs such as Corilagin, Emodin, Geniposidic acid, Auraptene.

Because FXR controls the synthesis, transport, and metabolism of BAs, and upregulates ABCB11 and multidrug resistance-associated protein 2(MRP2) to promote the secretion of BAs.

The fact that mutations in the ABCB11 gene in PFIC2 patients lead to extremely low biliary bile salt concentrations (<1% of normal).

When bile salt levels become elevated in hepatocytes, upregulating ABCB11 expression increases the eff lux of bile salts from hepatocytes to normalize cellular levels of bile salts.

The regulatory mechanism of BSEP expression and function can be briefly divided into two categories: transcriptional and post-transcriptional BSEP regulation.

If the ABCB11 structure is modified or its function is inhibited; the liver can accumulate excessive bile. This affects the regeneration of liver tissue and glucose homeostasis, leads to atherosclerosis, and even causes cancer.

Infants with jaundice associated with ABCB11 mutations are thought generally to have liver disease that persists and worsens.

Defects in ABCB11,cause progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of rare, autosomal recessive liver diseases of childhood.

The bile salt export pump (BSEP/ABCB11) is a liver-resident transporter protein,which plays an essential role in the enterohepatic circulation of the bile salts.

The bile acid(BA) that is exported to the intestine can be reabsorbed in the terminal ileum and returned to the liver through the portal vein system and enter the liver cells via the Na+ dependent taurocholic cotransporting polypeptide (NTCP) on the hepatocyte basolateral plasma membrane.They are subsequently secreted into the bile canaliculi through the bile salt export pump (BSEP) on the apical membrane of hepatocytes.

Secretion of bile salts by ABCB11 is essential for bile flow and for absorption of lipids and fat-soluble vitamins.