Protein: Phosphatidylcholine translocator ABCB4 (EC 7.6.2.1) (ATP-binding cassette sub-family B member 4) (Multidrug resistance protein 3) (P-glycoprotein 3) (P21439)
Organism: Homo sapiens (Human)
Function: 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).
Subcellular location: Cell membrane {ECO:0000269|PubMed:23468132, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}. Apical cell membrane {ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:24122873, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:8898203}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}. Membrane raft {ECO:0000269|PubMed:23468132}. Cytoplasm {ECO:0000269|PubMed:24045840}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250|UniProtKB:Q08201}. Note=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). {ECO:0000250|UniProtKB:P21440, ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:23468132}.
Interaction partners:
- Phospholipid-transporting ATPase IC
- Probable non-functional immunoglobulin heavy variable 3-16
- Ileal sodium/bile acid cotransporter
- Hepatic sodium/bile acid cotransporter
- Cytochrome P450 7A1
- Bile acid receptor
- Peroxisome proliferator-activated receptor alpha
- ATP-binding cassette sub-family C member 2
- Nuclear receptor subfamily 1 group I member 2
Sequence:
MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLGTIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYYSGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDDISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSAFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQSGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPVLFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVIAGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKSRLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIANGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAGEILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIANLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGAYLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSYSEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQPQILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTQNL