ABCB4
Function
Isoform 1
Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:17523162, PubMed:21820390, PubMed:23468132, PubMed:24594635, PubMed:24723470, PubMed:24806754, PubMed:31873305, PubMed:7957936, PubMed:8898203, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:28012258, PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (By similarity).
Involvement in disease
Cholestasis, progressive familial intrahepatic, 3
PFIC3
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC3 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Cholestasis of pregnancy, intrahepatic 3
ICP3
A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine.
None
The disease is caused by variants affecting the gene represented in this entry.
Gallbladder disease 1
GBD1
One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated (PubMed:24723470). Phosphorylation on Thr-34 is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner (PubMed:24723470). May be phosphorylated on Thr-44 and Ser-49 (PubMed:24723470).
Glycosylated (PubMed:17523162, PubMed:21820390, PubMed:24723470).
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Apical cell membrane
- Multi-pass membrane protein
- Membrane raft
- Cytoplasm
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (By similarity). Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner (PubMed:19674157). Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner (PubMed:15258199). Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132).
Alternative names
MDR3, PGY3, ABCB4, Phosphatidylcholine translocator ABCB4, ATP-binding cassette sub-family B member 4, Multidrug resistance protein 3, P-glycoprotein 3