Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ABCB4 (P21439) - Overview - Molecular Target Synopsis

Protein


ABCB4, Phosphatidylcholine translocator ABCB4
Enzyme Classification 7.6.2.2
UniProt P21439

Also Known as MDR3_HUMAN, ABCB4, MDR3, PGY3

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). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571, PubMed:28012258). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance. May interact with RACK1 (PubMed:19674157). Interacts with HAX1.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: ABCB4 is active in the following subcellular-locations: apical cell membrane, cell membrane, clathrin-coated vesicle, cytoplasm, cytoplasmic vesicle, membrane raft.
GO terms: ABCB4 is active in the following subcellular-locations: actin cytoskeleton, apical plasma membrane, clathrin-coated vesicle, cytoplasm, cytosol, extracellular exosome, focal adhesion, integral component of plasma membrane, intercellular canaliculus, membrane, membrane raft, nucleoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ABCB4 has gain in 10 cell-lines, loss in 1 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_2, TK_10, KM12

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-MEL-24, HT-144, Daudi

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


At greater than 75% identity similarity to ABCB4 there are:
2 structures (2 chains) solved
2 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

ABCB4 is solved in complex with the approved drug(s):

TA1/PACLITAXEL (6QEX_A),
CLR/CHOLESTEROL (6QEX_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ABCB4 has been screened with 6 compounds (6 bioactivities). (see details)