Names & Taxonomy
- Uniprot ID:
- P21439
- Entry Name:
- MDR3_HUMAN
- Status:
- reviewed
- Protein Names:
- Phosphatidylcholine translocator ABCB4 (ATP-binding cassette sub-family B member 4) (Multidrug resistance protein 3) (EC 3.6.3.44) (P-glycoprotein 3)
- Gene Names:
- ABCB4 MDR3 PGY3
- Gene Names Primary:
- ABCB4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1286
- Sequence:
- MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLGTIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYYSGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDDISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSAFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQSGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPVLFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVIAGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKSRLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIANGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAGEILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIANLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGAYLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSYSEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQPQILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTQNL
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
Function
- 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 (PubMed:7957936, PubMed:8898203, PubMed:9366571, PubMed:17523162, PubMed:23468132, PubMed:24806754, PubMed:24723470, PubMed:24594635, PubMed:21820390). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to fu rther 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). May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (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).
- Catalytic Activity:
- ATP + H(2)O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out).
- Enzyme Regulation:
- ENZYME REGULATION: Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:17523162, PubMed:23468132). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:17523162, PubMed:23468132).
- Cross Reference Drug Bank:
- DB01394 DB06414 DB06207
- Gene Ontology Go:
- apical plasma membrane
clathrin-coated vesicle
cytoplasm
extracellular exosome
integral component of plasma membrane
intercellular canaliculus
membrane
membrane raft
plasma membrane
ATP binding
ATPase activity, coupled to transmembrane movement of substances
phosphatidylcholine transporter activity
phosphatidylcholine-translocating ATPase activity
xenobiotic-transporting ATPase activity
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent
antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent
bile acid secretion
cellular lipid metabolic process
cellular response to bile acid
lipid homeostasis
lipid metabolic process
phospholipid translocation
positive regulation of antigen processing and presentation of peptide antigen via MHC class I
positive regulation of cholesterol transport
positive regulation of phospholipid translocation
positive regulation of phospholipid transport
response to drug
response to fenofibrate
small molecule metabolic process
transmembrane transport
transport - Gene Ontology Biological Process:
- antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent
bile acid secretion
cellular lipid metabolic process
cellular response to bile acid
lipid homeostasis
lipid metabolic process
phospholipid translocation
positive regulation of antigen processing and presentation of peptide antigen via MHC class I
positive regulation of cholesterol transport
positive regulation of phospholipid translocation
positive regulation of phospholipid transport
response to drug
response to fenofibrate
small molecule metabolic process
transmembrane transport
transport - Gene Ontology Molecular Function:
- ATPase activity, coupled to transmembrane movement of substances
ATP binding
phosphatidylcholine-translocating ATPase activity
phosphatidylcholine transporter activity
xenobiotic-transporting ATPase activity - Gene Ontology Cellular Component:
- apical plasma membrane
clathrin-coated vesicle
cytoplasm
extracellular exosome
integral component of plasma membrane
intercellular canaliculus
membrane
membrane raft
plasma membrane - Keywords:
- ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Disease mutation
Glycoprotein
Hydrolase
Intrahepatic cholestasis
Lipid transport
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Transmembrane
Transmembrane helix
Transport
Publication
- PubMed ID:
- 2906314 12853948 12690205 7893760 2892668 2002063 7957936 8898203 9366571 9419367 15258199 17523162 19674157 21820390 23468132 24122873 24806754 10767346 11313315 11313316 12671900 12891548 12746424 15077010 16763017 17726488 17264802 19261551 21119540 22331132 23533021 24045840 24723470 24594635