ABCB4

ABCB4 is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. ABCB4 is a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function.

ATP Binding Cassette Subfamily B Member 4

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. 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. 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. Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane. In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts. Does not confer multidrug resistance (By similarity).

Bile acid secretion
Cellular response to bile acid
Ceramide translocation
Lipid homeostasis
Lipid metabolic process
Phospholipid translocation
Positive regulation of cholesterol transport
Positive regulation of phospholipid translocation
Positive regulation of phospholipid transport
Regulation of metabolic process
Response to fenofibrate
Transmembrane transport

Cytoplasm; Cell membrane; Apical cell membrane; Membrane raft; 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. Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner. Localized preferentially in lipid nonraft domains of canalicular plasma membranes.

A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood.
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.
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.

Cytoplasmic: 1-50 aa
Helical: 51-73 aa
Extracellular: 74-118 aa
Helical: 119-139 aa
Cytoplasmic: 140-188 aa
Helical: 189-210 aa
Extracellular: 211-217 aa
Helical: 218-238 aa
Cytoplasmic: 239-296 aa
Helical: 297-318 aa
Extracellular: 319-332 aa
Helical: 333-354 aa
Cytoplasmic: 355-711 aa
Helical: 712-732 aa
Extracellular: 733-755 aa
Helical: 756-776 aa
Cytoplasmic: 777-831 aa
Helical: 832-852 aa
Extracellular: 853 aa
Helical: 854-873 aa
Cytoplasmic: 874-933 aa
Helical: 934-956 aa
Extracellular: 957-972 aa
Helical: 973-994 aa
Cytoplasmic: 995-1286 aa

Phosphorylated. 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. May be phosphorylated on Thr-44 and Ser-49.
Glycosylated