Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARalpha-mediated redistribution of ABCB4.
Bile salt-dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4.
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ABCB4-dependent PC availability promotes indirect cholesterol efflux.
"PC vesicles induced cholesterol diffusion from cell membrane, but
did not accept cholesterol from ABCB4."
Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4.
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RACK1 binds the isolated ABCB4 linker and regulates surface targeting; full-length co-immunoprecipitation was unsuccessful.
"The association of RACK1 with the linker region of ABCB4 was
further confirmed by GST-pulldown assay"
Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity.
Bile salt-stimulated phospholipid efflux mediated by ABCB4 localized in nonraft membranes.
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Most ABCB4 is nonraft; the original fractionation also detects a minor raft pool, and cell assays show rhodamine efflux.
"ABCB4 and ABCB1 were mainly distributed in
nonraft membranes."
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
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The study catalogs an exosome proteome from prostatic secretions in urine; the specific ABCB4 supplemental assignment remains unchecked.
"In pooled EPS-urine exosome
samples, ~900 proteins were detected."
Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction.
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NBD variants reduce PC release despite similar expression; stimulated cholesterol release can increase rather than decrease.
"both mutations
caused a reduction of phosphatidylcholine secretion compared with the wild-type
transfected cell lines."
Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion.
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Fenofibrate induces human ABCB4 expression via PPAR-alpha; functional PC secretion assays in this paper used rat hepatocytes.
"Fenofibrate significantly up-regulated MDR3
messenger RNA (mRNA) and protein expression in primary cultured human
hepatocytes"
Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity.
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Variant-specific loss of MDR3 expression or PC translocation correlates with PFIC3 severity.
"ABCB4 missense
mutations were phenotyped in vitro by assessing their effects on MDR3
expression, subcellular localisation, and phosphatidylcholine-translocating
activity."
Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations.
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Phosphorylation modulates ABCB4 secretion activity without necessarily altering apical targeting.
"ABCB4 activity is regulated by phosphorylation,
in particular, of N-terminal residues."
Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4.
Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770).
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ATP-binding-motif variants reach the plasma membrane yet have impaired PC secretion.
"the ABCB4 mutants were normally processed and targeted to the plasma
membrane, whereas their PC secretion activity was dramatically decreased."
Structure of the human lipid exporter ABCB4 in a lipid environment.
Phosphatidylcholine translocase: a physiological role for the mdr2 gene.
MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine.
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Human MDR3 translocates tested short-chain PC; the negative comparison concerns SM and GlcCer analogs, not direct free-ceramide transport.
"MDR3 cells exclusively
released a short-chain phosphatidylcholine."
ABC-family proteins mediated transport
ABCB4 transports PC from plasma membrane to extracellular region
Defective ABCB4 does not transport PC from plasma membrane to extracellular region
Structures of ABCB4 provide insight into phosphatidylcholine translocation.
Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4.
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ABCB4 can interact with some ABCB1 drug substrates; ATPase modulation alone should not be equated with direct flux for each compound.
"ABCB4 is described as an ATP-binding cassette (ABC) transporter that primarily
transports lipids of the phosphatidylcholine (PC) family"
Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease.
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Mouse Abcb4 disruption eliminates biliary phospholipids, defining a phospholipid-secretion requirement.
"Mice heterozygous
for the disrupted allele had no detectable liver pathology, but half the level
of phospholipid in bile."
Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse.
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Fibrate induction of mouse Abcb4 correlates with enhanced biliary phospholipid output without altered bile-acid output.
"In
treated animals, bile flow as well as cholesterol and bile acid outputs remained
unchanged."
Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes.
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The mouse study compares canalicular transport proteins under radixin loss; the principal mechanistic result concerns ABCC2/Mrp2.
"Mrp2 is decreased compared with other BCM
proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins."
Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells.
ABCB4 evidence review and source-access notes
ABCB4 Falcon deep research