ABCB11
Domain
Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
Function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269).
Involvement in disease
Cholestasis, progressive familial intrahepatic, 2
PFIC2
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC2 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Cholestasis, benign recurrent intrahepatic, 2
BRIC2
A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11.
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
Tissue Specificity
Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ.
Cellular localization
- Apical cell membrane
- Multi-pass membrane protein
- Recycling endosome membrane
- Multi-pass membrane protein
- Endosome
- Cell membrane
- Multi-pass membrane protein
- Internalized at the canalicular membrane through interaction with the adapter protein complex 2 (AP-2) (PubMed:22262466). At steady state, localizes in the canalicular membrane but is also present in recycling endosomes. ABCB11 constantly and rapidly exchanges between the two sites through tubulo-vesicles carriers that move along microtubules. Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway. Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (By similarity). Cell membrane expression is up-regulated by short- and medium-chain fatty acids (PubMed:20398791).
Alternative names
BSEP, ABCB11, Bile salt export pump, ATP-binding cassette sub-family B member 11