MDR3_MOUSE
ID MDR3_MOUSE Reviewed; 1276 AA.
AC P21440; B9EK77; Q6LCL9;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Phosphatidylcholine translocator ABCB4 {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000269|PubMed:7912658};
DE AltName: Full=ATP-binding cassette sub-family B member 4 {ECO:0000312|MGI:MGI:97569};
DE AltName: Full=Multidrug resistance protein 2 {ECO:0000303|PubMed:3405218};
DE AltName: Full=Multidrug resistance protein 3 {ECO:0000250|UniProtKB:P21439};
DE AltName: Full=P-glycoprotein 2 {ECO:0000250|UniProtKB:Q08201};
DE AltName: Full=P-glycoprotein 3 {ECO:0000250|UniProtKB:Q08201};
GN Name=Abcb4 {ECO:0000312|MGI:MGI:97569};
GN Synonyms=Mdr2 {ECO:0000303|PubMed:3405218}, Pgy-2,
GN Pgy2 {ECO:0000250|UniProtKB:Q08201};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3405218; DOI=10.1128/mcb.8.7.2770-2778.1988;
RA Gros P., Raymond M., Bell J., Housman D.;
RT "Cloning and characterization of a second member of the mouse mdr gene
RT family.";
RL Mol. Cell. Biol. 8:2770-2778(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
RC STRAIN=BALB/cJ;
RA Kirschner L.S., Horwitz S.B.;
RT "5'-end analysis of the murine mdr2 mRNA reveals complex and tissue-
RT specific processing.";
RL Submitted (DEC-1991) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-92.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=8759018; DOI=10.1093/nar/24.14.2829;
RA Kirschner L.S.;
RT "De novo generation of simple sequence during gene amplification.";
RL Nucleic Acids Res. 24:2829-2834(1996).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=2471060; DOI=10.1128/mcb.9.3.1346-1350.1989;
RA Croop J.M., Raymond M., Haber D., Devault A., Arceci R.J., Gros P.,
RA Housman D.E.;
RT "The three mouse multidrug resistance (mdr) genes are expressed in a
RT tissue-specific manner in normal mouse tissues.";
RL Mol. Cell. Biol. 9:1346-1350(1989).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=1969609; DOI=10.1128/mcb.10.4.1642-1651.1990;
RA Raymond M., Rose E., Housman D.E., Gros P.;
RT "Physical mapping, amplification, and overexpression of the mouse mdr gene
RT family in multidrug-resistant cells.";
RL Mol. Cell. Biol. 10:1642-1651(1990).
RN [8]
RP ABSENCE OF FUNCTION.
RX PubMed=1990275; DOI=10.1128/mcb.11.2.595-603.1991;
RA Buschman E., Gros P.;
RT "Functional analysis of chimeric genes obtained by exchanging homologous
RT domains of the mouse mdr1 and mdr2 genes.";
RL Mol. Cell. Biol. 11:595-603(1991).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=1381362; DOI=10.1016/s0021-9258(19)37157-1;
RA Buschman E., Arceci R.J., Croop J.M., Che M., Arias I.M., Housman D.E.,
RA Gros P.;
RT "mdr2 encodes P-glycoprotein expressed in the bile canalicular membrane as
RT determined by isoform-specific antibodies.";
RL J. Biol. Chem. 267:18093-18099(1992).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=8106172; DOI=10.1016/0092-8674(93)90380-9;
RA Smit J.J., Schinkel A.H., Oude Elferink R.P., Groen A.K., Wagenaar E.,
RA van Deemter L., Mol C.A., Ottenhoff R., van der Lugt N.M., van Roon M.A.;
RT "Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a
RT complete absence of phospholipid from bile and to liver disease.";
RL Cell 75:451-462(1993).
RN [11]
RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=7912658; DOI=10.1016/0092-8674(94)90446-4;
RA Ruetz S., Gros P.;
RT "Phosphatidylcholine translocase: a physiological role for the mdr2 gene.";
RL Cell 77:1071-1081(1994).
RN [12]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=7592705; DOI=10.1074/jbc.270.43.25388;
RA Ruetz S., Gros P.;
RT "Enhancement of Mdr2-mediated phosphatidylcholine translocation by the bile
RT salt taurocholate. Implications for hepatic bile formation.";
RL J. Biol. Chem. 270:25388-25395(1995).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7814632; DOI=10.1172/jci117658;
RA Oude Elferink R.P., Ottenhoff R., van Wijland M., Smit J.J., Schinkel A.H.,
RA Groen A.K.;
RT "Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the
RT mouse.";
RL J. Clin. Invest. 95:31-38(1995).
RN [14]
RP SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=8615769; DOI=10.1042/bj3140781;
RA Chianale J., Vollrath V., Wielandt A.M., Amigo L., Rigotti A., Nervi F.,
RA Gonzalez S., Andrade L., Pizarro M., Accatino L.;
RT "Fibrates induce mdr2 gene expression and biliary phospholipid secretion in
RT the mouse.";
RL Biochem. J. 314:781-786(1996).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8725158;
RA Oude Elferink R.P., Ottenhoff R., van Wijland M., Frijters C.M.,
RA van Nieuwkerk C., Groen A.K.;
RT "Uncoupling of biliary phospholipid and cholesterol secretion in mice with
RT reduced expression of mdr2 P-glycoprotein.";
RL J. Lipid Res. 37:1065-1075(1996).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9366571; DOI=10.1172/jci119799;
RA Crawford A.R., Smith A.J., Hatch V.C., Oude Elferink R.P., Borst P.,
RA Crawford J.M.;
RT "Hepatic secretion of phospholipid vesicles in the mouse critically depends
RT on mdr2 or MDR3 P-glycoprotein expression. Visualization by electron
RT microscopy.";
RL J. Clin. Invest. 100:2562-2567(1997).
RN [17]
RP INDUCTION.
RX PubMed=12381268; DOI=10.1042/bj20020981;
RA Kok T., Bloks V.W., Wolters H., Havinga R., Jansen P.L., Staels B.,
RA Kuipers F.;
RT "Peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated
RT regulation of multidrug resistance 2 (Mdr2) expression and function in
RT mice.";
RL Biochem. J. 369:539-547(2003).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21820390; DOI=10.1053/j.gastro.2011.07.042;
RA Groen A., Romero M.R., Kunne C., Hoosdally S.J., Dixon P.H., Wooding C.,
RA Williamson C., Seppen J., Van den Oever K., Mok K.S., Paulusma C.C.,
RA Linton K.J., Oude Elferink R.P.;
RT "Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in
RT maintaining canalicular membrane integrity.";
RL Gastroenterology 141:1927-1937(2011).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=23468132; DOI=10.1194/jlr.m032425;
RA Morita S.Y., Tsuda T., Horikami M., Teraoka R., Kitagawa S., Terada T.;
RT "Bile salt-stimulated phospholipid efflux mediated by ABCB4 localized in
RT nonraft membranes.";
RL J. Lipid Res. 54:1221-1230(2013).
CC -!- FUNCTION: Energy-dependent phospholipid efflux translocator that acts
CC as a positive regulator of biliary lipid secretion. Functions as a
CC floppase that translocates specifically phosphatidylcholine (PC) from
CC the inner to the outer leaflet of the canalicular membrane bilayer into
CC the canaliculi between hepatocytes. Translocation of PC makes the
CC biliary phospholipids available for extraction into the canaliculi
CC lumen by bile salt mixed micelles and therefore protects the biliary
CC tree from the detergent activity of bile salts (PubMed:8106172,
CC PubMed:7912658, PubMed:7592705, PubMed:7814632, PubMed:8725158,
CC PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine
CC (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to
CC nonraft membranes and to further enrichment of SM and cholesterol in
CC raft membranes in hepatocytes (By similarity). Required for proper
CC phospholipid bile formation (PubMed:8106172). Indirectly involved in
CC cholesterol efflux activity from hepatocytes into the canalicular lumen
CC in the presence of bile salts in an ATP-dependent manner
CC (PubMed:7814632, PubMed:8725158). May promote biliary phospholipid
CC secretion as canaliculi-containing vesicles from the canalicular plasma
CC membrane (PubMed:9366571). In cooperation with ATP8B1, functions to
CC protect hepatocytes from the deleterious detergent activity of bile
CC salts (PubMed:21820390). Does not confer multidrug resistance
CC (PubMed:1990275). {ECO:0000250|UniProtKB:P21439,
CC ECO:0000269|PubMed:1990275, ECO:0000269|PubMed:21820390,
CC ECO:0000269|PubMed:7592705, ECO:0000269|PubMed:7814632,
CC ECO:0000269|PubMed:7912658, ECO:0000269|PubMed:8106172,
CC ECO:0000269|PubMed:8725158, ECO:0000269|PubMed:9366571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:7912658};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a
CC 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:66272, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:7912658};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66273;
CC Evidence={ECO:0000269|PubMed:7912658};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O
CC = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:36439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64612, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P21439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36440;
CC Evidence={ECO:0000250|UniProtKB:P21439};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:38903, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P21439};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38904;
CC Evidence={ECO:0000250|UniProtKB:P21439};
CC -!- ACTIVITY REGULATION: Translocation activity is inhibited by the ATPase
CC inhibitor vanadate and the calcium channel blocker verapamil
CC (PubMed:7912658). Translocation activity is enhanced by the addition of
CC the bile salt taurocholate (PubMed:7592705).
CC {ECO:0000269|PubMed:7592705, ECO:0000269|PubMed:7912658}.
CC -!- SUBUNIT: May interact with RACK1. Interacts with HAX1.
CC {ECO:0000250|UniProtKB:P21439, ECO:0000250|UniProtKB:Q08201}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23468132,
CC ECO:0000269|PubMed:8106172, ECO:0000269|PubMed:8615769}; Multi-pass
CC membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}. Apical cell
CC membrane {ECO:0000269|PubMed:1381362}; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441}. Membrane raft
CC {ECO:0000250|UniProtKB:P21439}. Cytoplasm
CC {ECO:0000250|UniProtKB:P21439}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:Q08201}. Note=Transported from the Golgi
CC to the apical bile canalicular membrane in a RACK1-dependent manner.
CC Redistributed into pseudocanaliculi formed between cells in a
CC bezafibrate- or PPARA-dependent manner (By similarity). Localized at
CC the apical canalicular membrane of the epithelial cells lining the
CC lumen of the bile canaliculi and biliary ductules (PubMed:1381362,
CC PubMed:8106172, PubMed:8615769). Localized preferentially in lipid
CC nonraft domains of canalicular plasma membranes (PubMed:23468132).
CC {ECO:0000250|UniProtKB:P21439, ECO:0000269|PubMed:1381362,
CC ECO:0000269|PubMed:23468132, ECO:0000269|PubMed:8106172,
CC ECO:0000269|PubMed:8615769}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver (PubMed:1381362,
CC PubMed:8615769) (at protein level). Expressed in adrenal, liver,
CC muscle, spleen and heart (PubMed:2471060). Expressed in multidrug-
CC resistant cell lines (PubMed:1969609). {ECO:0000269|PubMed:1381362,
CC ECO:0000269|PubMed:1969609, ECO:0000269|PubMed:2471060,
CC ECO:0000269|PubMed:8615769}.
CC -!- INDUCTION: Up-regulated by compounds that cause peroxisome
CC proliferation, such as ciprofibrate and clofibrate (at protein level)
CC (PubMed:8615769). Up-regulated by compounds that cause peroxisome
CC proliferation, such as fenofibrate, ciprofibrate, clofibrate,
CC bezafibrate and gemfibrozil (PubMed:8615769, PubMed:12381268).
CC {ECO:0000269|PubMed:12381268, ECO:0000269|PubMed:8615769}.
CC -!- PTM: Phosphorylated. Phosphorylation is required for PC efflux
CC activity. Phosphorylation occurs on serine and threonine residues in a
CC protein kinase A- or C-dependent manner. May be phosphorylated on Thr-
CC 41 and Ser-46. {ECO:0000250|UniProtKB:P21439}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P21439}.
CC -!- DISRUPTION PHENOTYPE: Mice show severe necrotic damage of hepatocytes,
CC strong portal inflammation, proliferation and destruction of the
CC canalicular and small bile ductular tracts (PubMed:8106172). Display
CC almost complete reduction of biliary phospholipid secretion, although
CC bile salt secretion is normal (PubMed:8106172, PubMed:7814632,
CC PubMed:8725158, PubMed:9366571). Show also reduced cholesterol
CC secretion (PubMed:8106172, PubMed:9366571). Knockout mice lacking both
CC ABCB4 and ATP8B1 show lower hepatic damage compared with the single
CC ABCB4 knockout mice (PubMed:21820390). Display equivalent reduction of
CC biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout
CC mice (PubMed:21820390). Biliary cholesterol secretion is higher
CC compared to the single ABCB4 knockout mice (PubMed:21820390). Bile salt
CC secretion is normal in both single ABCB4 knockout mice and double ABCB4
CC and ATP8B1 knockout mice (PubMed:21820390). Biliary excretion of
CC canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is
CC strongly reduced compared to single ATP8B1 knockout mice
CC (PubMed:21820390). {ECO:0000269|PubMed:21820390,
CC ECO:0000269|PubMed:7814632, ECO:0000269|PubMed:8106172,
CC ECO:0000269|PubMed:8725158, ECO:0000269|PubMed:9366571}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
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DR EMBL; J03398; AAA39516.1; -; mRNA.
DR EMBL; CH466600; EDL14681.1; -; Genomic_DNA.
DR EMBL; BC150687; AAI50688.1; -; mRNA.
DR EMBL; M74151; AAA39515.1; -; Genomic_DNA.
DR EMBL; U46839; AAC52722.1; -; Genomic_DNA.
DR CCDS; CCDS19086.1; -.
DR PIR; A30409; DVMS2.
DR RefSeq; NP_032856.2; NM_008830.2.
DR AlphaFoldDB; P21440; -.
DR SMR; P21440; -.
DR BioGRID; 202139; 1.
DR STRING; 10090.ENSMUSP00000003717; -.
DR SwissLipids; SLP:000000362; -.
DR GlyGen; P21440; 2 sites.
DR iPTMnet; P21440; -.
DR PhosphoSitePlus; P21440; -.
DR jPOST; P21440; -.
DR MaxQB; P21440; -.
DR PaxDb; P21440; -.
DR PeptideAtlas; P21440; -.
DR PRIDE; P21440; -.
DR ProteomicsDB; 293448; -.
DR Antibodypedia; 3853; 227 antibodies from 33 providers.
DR DNASU; 18670; -.
DR Ensembl; ENSMUST00000003717; ENSMUSP00000003717; ENSMUSG00000042476.
DR GeneID; 18670; -.
DR KEGG; mmu:18670; -.
DR UCSC; uc008wkr.2; mouse.
DR CTD; 5244; -.
DR MGI; MGI:97569; Abcb4.
DR VEuPathDB; HostDB:ENSMUSG00000042476; -.
DR eggNOG; KOG0055; Eukaryota.
DR GeneTree; ENSGT00940000159418; -.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; P21440; -.
DR OMA; YIYLNYG; -.
DR OrthoDB; 186078at2759; -.
DR PhylomeDB; P21440; -.
DR TreeFam; TF105193; -.
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR BioGRID-ORCS; 18670; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Abcb4; mouse.
DR PRO; PR:P21440; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P21440; protein.
DR Bgee; ENSMUSG00000042476; Expressed in left lobe of liver and 170 other tissues.
DR ExpressionAtlas; P21440; baseline and differential.
DR Genevisible; P21440; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0046581; C:intercellular canaliculus; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0099038; F:ceramide floppase activity; IBA:GO_Central.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; ISS:UniProtKB.
DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IBA:GO_Central.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0032782; P:bile acid secretion; IMP:UniProtKB.
DR GO; GO:1903413; P:cellular response to bile acid; ISS:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0045332; P:phospholipid translocation; ISO:MGI.
DR GO; GO:0032376; P:positive regulation of cholesterol transport; ISS:UniProtKB.
DR GO; GO:0061092; P:positive regulation of phospholipid translocation; ISS:UniProtKB.
DR GO; GO:2001140; P:positive regulation of phospholipid transport; ISS:UniProtKB.
DR GO; GO:1901557; P:response to fenofibrate; IDA:UniProtKB.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030275; MDR3.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR PANTHER; PTHR24221:SF241; PTHR24221:SF241; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cytoplasm; Cytoplasmic vesicle; Glycoprotein;
KW Lipid transport; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1276
FT /note="Phosphatidylcholine translocator ABCB4"
FT /id="PRO_0000093337"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 48..70
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 71..115
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 137..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 186..207
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 208..212
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 213..235
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 236..293
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 294..315
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 316..329
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 330..351
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 352..708
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 709..729
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 730..752
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 753..773
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 774..828
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 829..849
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 850
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 851..870
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 871..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 931..953
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 954..969
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 970..991
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 992..1276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 54..356
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 391..627
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 708..996
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1031..1269
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 622..646
FT /note="Interaction with HAX1"
FT /evidence="ECO:0000250"
FT BINDING 403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21439"
FT BINDING 429..434
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21439,
FT ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 474
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21439"
FT BINDING 533
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21439"
FT BINDING 1043
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21439"
FT BINDING 1068..1074
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21439,
FT ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21439"
FT BINDING 1174..1176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21439,
FT ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 257
FT /note="L -> P (in Ref. 1; AAA39516)"
FT /evidence="ECO:0000305"
FT CONFLICT 828
FT /note="R -> K (in Ref. 1; AAA39516)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1276 AA; 140377 MW; 30BC72EDDFA4388C CRC64;
MDLEAARNGT ARRLDGDFEL GSISNQGREK KKKVNLIGLL TLFRYSDWQD KLFMFLGTLM
AIAHGSGLPL MMIVFGEMTD KFVDNTGNFS LPVNFSLSML NPGRILEEEM TRYAYYYSGL
GGGVLVAAYI QVSFWTLAAG RQIKKIRQKF FHAILRQEMG WFDIKGTTEL NTRLTDDVSK
ISEGIGDKVG MFFQAIATFF AGFIVGFIRG WKLTLVIMAI SPILGLSTAV WAKILSTFSD
KELAAYAKAG AVAEEALGAI RTVIAFGGQN KELERYQKHL ENAKKIGIKK AISANISMGI
AFLLIYASYA LAFWYGSTLV ISKEYTIGNA MTVFFSILIG AFSVGQAAPC IDAFANARGA
AYVIFDIIDN NPKIDSFSER GHKPDNIKGN LEFSDVHFSY PSRANIKILK GLNLKVKSGQ
TVALVGNSGC GKSTTVQLLQ RLYDPTEGKI SIDGQDIRNF NVRCLREIIG VVSQEPVLFS
TTIAENIRYG RGNVTMDEIE KAVKEANAYD FIMKLPQKFD TLVGDRGAQL SGGQKQRIAI
ARALVRNPKI LLLDEATSAL DTESEAEVQA ALDKAREGRT TIVIAHRLST IRNADVIAGF
EDGVIVEQGS HSELMKKEGI YFRLVNMQTA GSQILSEEFE VELSDEKAAG DVAPNGWKAR
IFRNSTKKSL KSPHQNRLDE ETNELDANVP PVSFLKVLKL NKTEWPYFVV GTVCAIANGA
LQPAFSIILS EMIAIFGPGD DAVKQQKCNM FSLVFLGLGV LSFFTFFLQG FTFGKAGEIL
TTRLRSMAFK AMLRQDMSWF DDHKNSTGAL STRLATDAAQ VQGATGTRLA LIAQNTANLG
TGIIISFIYG WQLTLLLLSV VPFIAVAGIV EMKMLAGNAK RDKKEMEAAG KIATEAIENI
RTVVSLTQER KFESMYVEKL HGPYRNSVRK AHIYGITFSI SQAFMYFSYA GCFRFGSYLI
VNGHMRFKDV ILVFSAIVLG AVALGHASSF APDYAKAKLS AAYLFSLFER QPLIDSYSGE
GLWPDKFEGS VTFNEVVFNY PTRANVPVLQ GLSLEVKKGQ TLALVGSSGC GKSTVVQLLE
RFYDPMAGSV LLDGQEAKKL NVQWLRAQLG IVSQEPILFD CSIAENIAYG DNSRVVPHDE
IVRAAKEANI HPFIETLPQK YNTRVGDKGT QLSGGQKQRI AIARALIRQP RVLLLDEATS
ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VIENGKVKEH GTHQQLLAQK
GIYFSMVNIQ AGTQNL
