Gene Symbol: Abcb4
Description: ATP binding cassette subfamily B member 4
Alias: Mdr2, Pgy3, phosphatidylcholine translocator ABCB4, ATP-binding cassette sub-family B (MDR/TAP) member 4 (P-glycoprotein 3/ multidrug resistance 2), ATP-binding cassette sub-family B member 4, ATP-binding cassette, sub-family B (MDR/TAP), member 4 (P-glycoprotein 3/ multidrug resistance 2), ATP-binding cassette, subfamily B (MDR/TAP), member 4, P-glycoprotein 2, P-glycoprotein 3, P-glycoprotein 3/ multidrug resistance 2, multidrug resistance protein 2, multidrug resistance protein 3
Species: rat
Products:     Abcb4

Top Publications

  1. Kipp H, Arias I. Newly synthesized canalicular ABC transporters are directly targeted from the Golgi to the hepatocyte apical domain in rat liver. J Biol Chem. 2000;275:15917-25 pubmed
    ..we compared membrane targeting of newly synthesized canalicular ABC (ATP-binding cassette) transporters MDR1, MDR2, and SPGP (sister of P-glycoprotein) with that of cCAM105...
  2. Ortiz D, Moseley J, Calderon G, Swift A, Li S, Arias I. 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. J Biol Chem. 2004;279:32761-70 pubmed
    ATP-binding cassette (ABC)-type proteins are essential for bile formation in vertebrate liver. BSEP, MDR1, MDR2, and MRP2 ABC transporters are targeted to the apical (canalicular) membrane of hepatocytes where they execute ATP-dependent ..
  3. Andress E, Nicolaou M, Romero M, Naik S, Dixon P, Williamson C, et al. Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4. Hepatology. 2014;59:1921-31 pubmed publisher
    b>ABCB4 flops phosphatidylcholine into the bile canaliculus to protect the biliary tree from the detergent activity of bile salts...
  4. Degiorgio D, Corsetto P, Rizzo A, Colombo C, Seia M, Costantino L, et al. Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction. Eur J Hum Genet. 2014;22:633-9 pubmed publisher
    The ABCB4 gene encodes for MDR3, a protein that translocates phosphatidylcholine from the inner to the outer leaflet of the hepatocanalicular membrane; its deficiency favors the formation of 'toxic bile'...
  5. Smit J, Schinkel A, Oude Elferink R, Groen A, Wagenaar E, van Deemter L, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell. 1993;75:451-62 pubmed
    ..The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, ..
  6. Aleksandrova M, Kushnareva N, Smirnova O. Manifestation of multidrug resistance protein 3 (MRP3) in liver and kidney cells in cholestasis: effects of hyperprolactinemia. Bull Exp Biol Med. 2013;154:508-11 pubmed
    ..It was hypothesized that prolactin produced a direct effect on mrp3 expression in cholangiocytes. ..
  7. Paulusma C, Bosma P, Zaman G, Bakker C, Otter M, Scheffer G, et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science. 1996;271:1126-8 pubmed
    ..In the TR(-) rat, a single-nucleotide deletion in this gene resulted in a reduced messenger RNA level and absence of the protein. It is likely that this mutation accounts for the TR(-) phenotype...
  8. Chianale J, Vollrath V, Wielandt A, Amigo L, Rigotti A, Nervi F, et al. Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse. Biochem J. 1996;314 ( Pt 3):781-6 pubmed
    Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids...
  9. Mei D, Li J, Liu H, Liu L, Wang X, Guo H, et al. Induction of multidrug resistance-associated protein 2 in liver, intestine and kidney of streptozotocin-induced diabetic rats. Xenobiotica. 2012;42:709-18 pubmed publisher
    ..Diabetes may enhance Mrp2 function and expression in liver, kidney and intestine, which might be due to insulin deficiency, increased TBA and conjugated bilirubin. ..

More Information


  1. Ikebuchi Y, Takada T, Ito K, Yoshikado T, Anzai N, Kanai Y, et al. Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4. Hepatol Res. 2009;39:1091-107 pubmed publisher
    b>Multidrug resistance protein 3 (MDR3/ABCB4), located on the bile canalicular membrane of hepatocytes, is responsible for the translocation of phosphatidylcholine across the plasma membrane, and its hereditary defect causes liver disorders,..
  2. Hyogo H, Tazuma S, Nishioka T, Ochi H, Yamaguchi A, Numata Y, et al. Phospholipid alterations in hepatocyte membranes and transporter protein changes in cholestatic rat model. Dig Dis Sci. 2001;46:2089-97 pubmed
    ..By 6 hr after bile duct ligation, we found a clear increase of mdr2 and bsep mRNA...
  3. Hagenbuch B, Gao B, Meier P. Transport of xenobiotics across the blood-brain barrier. News Physiol Sci. 2002;17:231-4 pubmed
    ..Members of the drug transporter families MDR, MRP, and OATP have been identified in the BBB, and a detailed characterization of the involved proteins is now required to target drugs more efficiently to the brain. ..
  4. Luttringer O, Theil F, Lave T, Wernli Kuratli K, Guentert T, de Saizieu A. Influence of isolation procedure, extracellular matrix and dexamethasone on the regulation of membrane transporters gene expression in rat hepatocytes. Biochem Pharmacol. 2002;64:1637-50 pubmed
    ..However, adding DEX to the incubation medium in SPC resulted in an up-regulation of mdr2, oatp2 and mrp2 in a concentration-dependent way for the two latter genes, whereas mdr1b and mrp3 expression were ..
  5. van Waarde W, Verkade H, Wolters H, Havinga R, Baller J, Bloks V, et al. Differential effects of streptozotocin-induced diabetes on expression of hepatic ABC-transporters in rats. Gastroenterology. 2002;122:1842-52 pubmed
    ..Diabetes mellitus is associated with changes in bile formation. The aim of our study was to investigate the molecular basis for these changes in rats with experimentally induced diabetes...
  6. Hawkins B, Sykes D, Miller D. Rapid, reversible modulation of blood-brain barrier P-glycoprotein transport activity by vascular endothelial growth factor. J Neurosci. 2010;30:1417-25 pubmed publisher
  7. Morita S, Kobayashi A, Takanezawa Y, Kioka N, Handa T, Arai H, et al. Bile salt-dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4. Hepatology. 2007;46:188-99 pubmed
    Human ABCB4 (multidrug resistance [MDR]3 P-glycoprotein) is expressed in the canalicular membrane of the hepatocyte...
  8. Zhang Y, Li W, Vore M. Translational regulation of rat multidrug resistance-associated protein 2 expression is mediated by upstream open reading frames in the 5' untranslated region. Mol Pharmacol. 2007;71:377-83 pubmed
    ..We conclude that among the uORFs in the Mrp2 5'UTR, the uORF starting at nucleotide -109 probably plays an important role in the regulation of Mrp2 protein expression...
  9. Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, et al. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002;31:320-5 pubmed human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury...
  10. Deuchars K, Duthie M, Ling V. Identification of distinct P-glycoprotein gene sequences in rat. Biochim Biophys Acta. 1992;1130:157-65 pubmed
    ..We have also isolated a fourth clone which contains only a short, but highly conserved P-glycoprotein domain. This clone appears not be a member of the P-glycoprotein gene family, and its relationship to P-glycoprotein is unknown. ..
  11. Shih D, Bussen M, Sehayek E, Ananthanarayanan M, Shneider B, Suchy F, et al. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet. 2001;27:375-82 pubmed
    ..Our studies demonstrate that Tcf1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid and HDL-cholesterol metabolism. ..
  12. Hooiveld G, Vos T, Scheffer G, van Goor H, Koning H, Bloks V, et al. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats. Gastroenterology. 1999;117:678-87 pubmed
    Biliary cholesterol secretion is coupled to that of phospholipids in a process controlled by mdr2 P-glycoprotein activity and bile salt secretion...
  13. de Vree J, Jacquemin E, Sturm E, Cresteil D, Bosma P, Aten J, et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci U S A. 1998;95:282-7 pubmed
    Class III multidrug resistance (MDR) P-glycoproteins (P-gp), mdr2 in mice and MDR3 in man, mediate the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte...
  14. van Helvoort A, Smith A, Sprong H, Fritzsche I, Schinkel A, Borst P, et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell. 1996;87:507-17 pubmed
    ..Since no vesicular secretion occurs at 15 degrees C, the short-chain lipids must have been translocated by the Pgps across the plasma membrane before extraction into the medium by the lipid-acceptor albumin...
  15. Furuya K, Gebhardt R, Schuetz E, Schuetz J. Isolation of rat pgp3 cDNA: evidence for gender and zonal regulation of expression in the liver. Biochim Biophys Acta. 1994;1219:636-44 pubmed
    ..Our results also demonstrate heterogeneity of hepatic rat pgp3 gene expression, which is influenced by both gender and by acinar location. ..
  16. Brown P, Thorgeirsson S, Silverman J. Cloning and regulation of the rat mdr2 gene. Nucleic Acids Res. 1993;21:3885-91 pubmed
    We have cloned the complete cDNA encoding the rat mdr2 gene by a combination of library screening and the polymerase chain reaction...
  17. Buschman E, Gros P. Functional analysis of chimeric genes obtained by exchanging homologous domains of the mouse mdr1 and mdr2 genes. Mol Cell Biol. 1991;11:595-603 pubmed
    ..In the same assay, a full-length cDNA clone for a closely related member of the mouse mdr gene family, mdr2, fails to confer multidrug resistance...