MDR3_HUMAN
ID MDR3_HUMAN Reviewed; 1286 AA.
AC P21439; A0A2V7; A4D1D3; A4D1D4; A4D1D5; D6W5P3; D6W5P4; Q14813;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Phosphatidylcholine translocator ABCB4 {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000250|UniProtKB:P21440};
DE AltName: Full=ATP-binding cassette sub-family B member 4 {ECO:0000312|HGNC:HGNC:45};
DE AltName: Full=Multidrug resistance protein 3 {ECO:0000303|PubMed:2892668};
DE AltName: Full=P-glycoprotein 3 {ECO:0000250|UniProtKB:Q08201};
GN Name=ABCB4 {ECO:0000312|HGNC:HGNC:45};
GN Synonyms=MDR3 {ECO:0000303|PubMed:2892668}, PGY3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=2906314; DOI=10.1016/0378-1119(88)90057-1;
RA van der Bliek A.M., Kooiman P.M., Schneider C., Borst P.;
RT "Sequence of mdr3 cDNA encoding a human P-glycoprotein.";
RL Gene 71:401-411(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GBD1 ASP-528 AND GLN-788, AND
RP VARIANTS VAL-238; VAL-263; GLN-590; ASN-651 AND GLY-652.
RG NIEHS SNPs program;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-72 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7893760; DOI=10.1016/0167-4781(94)00214-n;
RA Smit J.J., Mol C.A., van Deemter L., Wagenaar E., Schinkel A.H., Borst P.;
RT "Characterization of the promoter region of the human MDR3 P-glycoprotein
RT gene.";
RL Biochim. Biophys. Acta 1261:44-56(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 856-1286 (ISOFORM 1), AND ALTERNATIVE
RP SPLICING.
RX PubMed=2892668;
RA van der Bliek A.M., Baas F., ten Houte de Lange T., Kooiman P.M.,
RA van der Velde-Koerts T., Borst P.;
RT "The human mdr3 gene encodes a novel P-glycoprotein homologue and gives
RT rise to alternatively spliced mRNAs in liver.";
RL EMBO J. 6:3325-3331(1987).
RN [8]
RP GENE STRUCTURE.
RX PubMed=2002063; DOI=10.1016/s0021-9258(19)67788-4;
RA Lincke C.R., Smit J.J.M., van der Velde-Koerts T., Borst P.;
RT "Structure of the human MDR3 gene and physical mapping of the human MDR
RT locus.";
RL J. Biol. Chem. 266:5303-5310(1991).
RN [9]
RP FUNCTION.
RX PubMed=7957936; DOI=10.1016/0014-5793(94)01135-4;
RA Smith A.J., Timmermans-Hereijgers J.L., Roelofsen B., Wirtz K.W.,
RA van Blitterswijk W.J., Smit J.J., Schinkel A.H., Borst P.;
RT "The human MDR3 P-glycoprotein promotes translocation of
RT phosphatidylcholine through the plasma membrane of fibroblasts from
RT transgenic mice.";
RL FEBS Lett. 354:263-266(1994).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=8898203; DOI=10.1016/s0092-8674(00)81370-7;
RA van Helvoort A., Smith A.J., Sprong H., Fritzsche I., Schinkel A.H.,
RA Borst P., van Meer G.;
RT "MDR1 P-glycoprotein is a lipid translocase of broad specificity, while
RT MDR3 P-glycoprotein specifically translocates phosphatidylcholine.";
RL Cell 87:507-517(1996).
RN [11]
RP FUNCTION.
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 [12]
RP INVOLVEMENT IN PFIC3.
RX PubMed=9419367; DOI=10.1073/pnas.95.1.282;
RA de Vree J.M.L., Jacquemin E., Sturm E., Cresteil D., Bosma P.J., Aten J.,
RA Deleuze J.-F., Desrochers M., Burdelski M., Bernard O.,
RA Oude Elferink R.P.J., Hadchouel M.;
RT "Mutations in the MDR3 gene cause progressive familial intrahepatic
RT cholestasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:282-287(1998).
RN [13]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=15258199; DOI=10.1194/jlr.m400132-jlr200;
RA Shoda J., Inada Y., Tsuji A., Kusama H., Ueda T., Ikegami T., Suzuki H.,
RA Sugiyama Y., Cohen D.E., Tanaka N.;
RT "Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2
RT cells by PPARalpha-mediated redistribution of ABCB4.";
RL J. Lipid Res. 45:1813-1825(2004).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, GLYCOSYLATION, AND MUTAGENESIS OF LYS-435
RP AND LYS-1075.
RX PubMed=17523162; DOI=10.1002/hep.21591;
RA Morita S.Y., Kobayashi A., Takanezawa Y., Kioka N., Handa T., Arai H.,
RA Matsuo M., Ueda K.;
RT "Bile salt-dependent efflux of cellular phospholipids mediated by ATP
RT binding cassette protein B4.";
RL Hepatology 46:188-199(2007).
RN [15]
RP INTERACTION WITH RACK1, AND SUBCELLULAR LOCATION.
RX PubMed=19674157; DOI=10.1111/j.1872-034x.2009.00544.x;
RA Ikebuchi Y., Takada T., Ito K., Yoshikado T., Anzai N., Kanai Y.,
RA Suzuki H.;
RT "Receptor for activated C-kinase 1 regulates the cellular localization and
RT function of ABCB4.";
RL Hepatol. Res. 39:1091-1107(2009).
RN [16]
RP FUNCTION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
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 [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
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).
RN [18]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=24122873; DOI=10.1002/hep.26894;
RA Ghonem N.S., Ananthanarayanan M., Soroka C.J., Boyer J.L.;
RT "Peroxisome proliferator-activated receptor alpha activates human multidrug
RT resistance transporter 3/ATP-binding cassette protein subfamily B4
RT transcription and increases rat biliary phosphatidylcholine secretion.";
RL Hepatology 59:1030-1042(2014).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PFIC3 VAL-286
RP AND PHE-320, AND MUTAGENESIS OF ALA-953.
RX PubMed=24806754; DOI=10.1002/hep.26970;
RA Andress E.J., Nicolaou M., Romero M.R., Naik S., Dixon P.H., Williamson C.,
RA Linton K.J.;
RT "Molecular mechanistic explanation for the spectrum of cholestatic disease
RT caused by the S320F variant of ABCB4.";
RL Hepatology 59:1921-1931(2014).
RN [20] {ECO:0007744|PDB:6S7P}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH ATP,
RP FUNCTION, CATALYTIC ACTIVITY (ISOFORM 2), MUTAGENESIS OF GLU-558; VAL-985;
RP HIS-989 AND ALA-990, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=31873305; DOI=10.1038/s41594-019-0354-3;
RA Olsen J.A., Alam A., Kowal J., Stieger B., Locher K.P.;
RT "Structure of the human lipid exporter ABCB4 in a lipid environment.";
RL Nat. Struct. Biol. 27:62-70(2020).
RN [21]
RP VARIANT ICP3 ASP-546, AND CHARACTERIZATION OF VARIANT ICP3 ASP-546.
RX PubMed=10767346; DOI=10.1093/hmg/9.8.1209;
RA Dixon P.H., Weerasekera N., Linton K.J., Donaldson O., Chambers J.,
RA Egginton E., Weaver J., Nelson-Piercy C., de Swiet M., Warnes G., Elias E.,
RA Higgins C.F., Johnston D.G., McCarthy M.I., Williamson C.;
RT "Heterozygous MDR3 missense mutation associated with intrahepatic
RT cholestasis of pregnancy: evidence for a defect in protein trafficking.";
RL Hum. Mol. Genet. 9:1209-1217(2000).
RN [22]
RP VARIANTS PFIC3 ARG-138; ILE-346; GLY-395; ALA-424; MET-425; PHE-541;
RP ARG-556; GLY-564; SER-711 AND SER-983, AND VARIANT GLY-652.
RX PubMed=11313315; DOI=10.1053/gast.2001.23984;
RA Jacquemin E., De Vree J.M.L., Cresteil D., Sokal E.M., Sturm E., Dumont M.,
RA Scheffer G.L., Paul M., Burdelski M., Bosma P.J., Bernard O., Hadchouel M.,
RA Elferink R.P.;
RT "The wide spectrum of multidrug resistance 3 deficiency: from neonatal
RT cholestasis to cirrhosis of adulthood.";
RL Gastroenterology 120:1448-1458(2001).
RN [23]
RP VARIANTS GBD1 PHE-320 AND SER-1168, AND VARIANT ALA-175.
RX PubMed=11313316; DOI=10.1053/gast.2001.23947;
RA Rosmorduc O., Hermelin B., Poupon R.;
RT "MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder
RT cholesterol cholelithiasis.";
RL Gastroenterology 120:1459-1467(2001).
RN [24]
RP VARIANT PFIC3 ASP-535.
RX PubMed=12671900; DOI=10.1053/gast.2003.50144;
RA Lucena J.-F., Herrero J.I., Quiroga J., Sangro B., Garcia-Foncillas J.,
RA Zabalegui N., Sola J., Herraiz M., Medina J.F., Prieto J.;
RT "A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis
RT of pregnancy, and adulthood biliary cirrhosis.";
RL Gastroenterology 124:1037-1042(2003).
RN [25]
RP VARIANTS GBD1 ILE-165; THR-301; PHE-320; ASP-528; GLN-591; GLN-788 AND
RP SER-1168, AND VARIANTS ALA-175; GLN-590; GLY-652; SER-742 AND THR-934.
RX PubMed=12891548; DOI=10.1016/s0016-5085(03)00898-9;
RA Rosmorduc O., Hermelin B., Boelle P.Y., Parc R., Taboury J., Poupon R.;
RT "ABCB4 gene mutation-associated cholelithiasis in adults.";
RL Gastroenterology 125:452-459(2003).
RN [26]
RP VARIANT ICP3 LYS-150, AND VARIANT GLY-652.
RX PubMed=12746424; DOI=10.1136/jmg.40.5.e70;
RA Muellenbach R., Linton K.J., Wiltshire S., Weerasekera N., Chambers J.,
RA Elias E., Higgins C.F., Johnston D.G., McCarthy M.I., Williamson C.;
RT "ABCB4 gene sequence variation in women with intrahepatic cholestasis of
RT pregnancy.";
RL J. Med. Genet. 40:E70-E70(2003).
RN [27]
RP VARIANTS ALA-175; GLY-652 AND MET-775, AND VARIANTS ICP3 PHE-320; ASP-528
RP AND GLU-762.
RX PubMed=15077010; DOI=10.1097/00008571-200402000-00003;
RA Pauli-Magnus C., Lang T., Meier Y., Zodan-Marin T., Jung D., Breymann C.,
RA Zimmermann R., Kenngott S., Beuers U., Reichel C., Kerb R., Penger A.,
RA Meier P.J., Kullak-Ublick G.A.;
RT "Sequence analysis of bile salt export pump (ABCB11) and multidrug
RT resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic
RT cholestasis of pregnancy.";
RL Pharmacogenetics 14:91-102(2004).
RN [28]
RP VARIANTS GLU-87; SER-95; ALA-175; VAL-367; GLY-450; GLN-590 AND GLY-652.
RX PubMed=16763017; DOI=10.1124/dmd.105.008854;
RA Lang T., Haberl M., Jung D., Drescher A., Schlagenhaufer R., Keil A.,
RA Mornhinweg E., Stieger B., Kullak-Ublick G.A., Kerb R.;
RT "Genetic variability, haplotype structures, and ethnic diversity of hepatic
RT transporters MDR3 (ABCB4) and bile salt export pump (ABCB11).";
RL Drug Metab. Dispos. 34:1582-1599(2006).
RN [29]
RP VARIANTS PFIC3 GLU-126; PRO-250; VAL-286; PHE-320; LEU-357; VAL-364;
RP HIS-403; ALA-475; THR-511; LYS-558; ALA-593; VAL-630; PRO-701; ILE-715;
RP GLU-723; THR-726; VAL-737; ASP-840; SER-954 AND THR-1193, AND VARIANTS
RP ALA-175; GLN-590 AND MET-775.
RX PubMed=17726488; DOI=10.1038/sj.ejhg.5201908;
RA Degiorgio D., Colombo C., Seia M., Porcaro L., Costantino L., Zazzeron L.,
RA Bordo D., Coviello D.A.;
RT "Molecular characterization and structural implications of 25 new ABCB4
RT mutations in progressive familial intrahepatic cholestasis type 3
RT (PFIC3).";
RL Eur. J. Hum. Genet. 15:1230-1238(2007).
RN [30]
RP VARIANTS ALA-175; GLN-590; GLY-652; LEU-764 AND GLN-1082.
RX PubMed=17264802; DOI=10.1097/01.fpc.0000230418.28091.76;
RA Lang C., Meier Y., Stieger B., Beuers U., Lang T., Kerb R.,
RA Kullak-Ublick G.A., Meier P.J., Pauli-Magnus C.;
RT "Mutations and polymorphisms in the bile salt export pump and the multidrug
RT resistance protein 3 associated with drug-induced liver injury.";
RL Pharmacogenet. Genomics 17:47-60(2007).
RN [31]
RP VARIANTS GLN-590 AND GLY-652.
RX PubMed=19261551; DOI=10.1016/j.dld.2008.12.101;
RA Tavian D., Degiorgio D., Roncaglia N., Vergani P., Cameroni I., Colombo R.,
RA Coviello D.A.;
RT "A new splicing site mutation of the ABCB4 gene in intrahepatic cholestasis
RT of pregnancy with raised serum gamma-GT.";
RL Dig. Liver Dis. 41:671-675(2009).
RN [32]
RP VARIANTS PFIC3 ARG-70; VAL-73; PHE-320 AND HIS-403, AND VARIANT GLY-652.
RX PubMed=21119540; DOI=10.1097/mpg.0b013e3181f50363;
RA Colombo C., Vajro P., Degiorgio D., Coviello D.A., Costantino L.,
RA Tornillo L., Motta V., Consonni D., Maggiore G., Balli F., Berardi S.,
RA Calacoci M., Castellano E., Marazzi M.G., Gaslini G., D'Antiga L.,
RA Ferretti E., Giannini A., Indolfi G., Iorio R., Martelossi S., Moretti C.,
RA Nebbia G., Oliveri F., Poggiani C., Raggi M., Riva S., Sciveres M.,
RA Torre G., Zancan L.;
RT "Clinical features and genotype-phenotype correlations in children with
RT progressive familial intrahepatic cholestasis type 3 related to ABCB4
RT mutations.";
RL J. Pediatr. Gastroenterol. Nutr. 52:73-83(2011).
RN [33]
RP VARIANTS GBD1 MET-34; GLY-47; VAL-286 AND ASP-528, AND VARIANTS GLN-47;
RP ALA-175; PHE-320; GLN-406; MET-775 AND THR-964.
RX PubMed=22331132; DOI=10.1007/s00428-012-1202-6;
RA Wendum D., Barbu V., Rosmorduc O., Arrive L., Flejou J.F., Poupon R.;
RT "Aspects of liver pathology in adult patients with MDR3/ABCB4 gene
RT mutations.";
RL Virchows Arch. 460:291-298(2012).
RN [34]
RP VARIANTS GBD1 GLY-47; HIS-71; VAL-73; CYS-78; PHE-99; SER-124; SER-154;
RP ILE-165; VAL-286; THR-301; PHE-320; GLY-406; SER-510; THR-511; LYS-513;
RP ASP-528; PHE-541; HIS-545; HIS-549; THR-589; GLN-591; MET-593; LYS-647;
RP LEU-726; LEU-729; GLN-788; VAL-975 AND TRP-1084, AND VARIANTS ALA-175;
RP GLN-590 AND THR-934.
RX PubMed=23533021; DOI=10.1002/hep.26424;
RA Poupon R., Rosmorduc O., Boelle P.Y., Chretien Y., Corpechot C.,
RA Chazouilleres O., Housset C., Barbu V.;
RT "Genotype-phenotype relationships in the low-phospholipid-associated
RT cholelithiasis syndrome: a study of 156 consecutive patients.";
RL Hepatology 58:1105-1110(2013).
RN [35]
RP VARIANT PFIC3 ARG-481, CHARACTERIZATION OF VARIANTS PFIC3 HIS-403 AND
RP ARG-481, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24045840; DOI=10.1038/ejhg.2013.214;
RA Degiorgio D., Corsetto P.A., Rizzo A.M., Colombo C., Seia M.,
RA Costantino L., Montorfano G., Tomaiuolo R., Bordo D., Sansanelli S., Li M.,
RA Tavian D., Rastaldi M.P., Coviello D.A.;
RT "Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein
RT targeting to the plasma membrane but promote MDR3 dysfunction.";
RL Eur. J. Hum. Genet. 22:633-639(2014).
RN [36]
RP VARIANTS GBD1 MET-34 AND GLY-47, CHARACTERIZATION OF VARIANTS GBD1 MET-34
RP AND GLY-47, FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-34,
RP GLYCOSYLATION, MUTAGENESIS OF THR-34; THR-44 AND SER-49, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=24723470; DOI=10.1002/hep.27170;
RA Gautherot J., Delautier D., Maubert M.A., Ait-Slimane T., Bolbach G.,
RA Delaunay J.L., Durand-Schneider A.M., Firrincieli D., Barbu V.,
RA Chignard N., Housset C., Maurice M., Falguieres T.;
RT "Phosphorylation of ABCB4 impacts its function: insights from disease-
RT causing mutations.";
RL Hepatology 60:610-621(2014).
RN [37]
RP VARIANTS PFIC3 ARG-68; MET-201; HIS-459; LEU-479; PRO-978 AND LYS-1125,
RP CHARACTERIZATION OF VARIANTS PFIC3 ARG-68; MET-201; HIS-459; LEU-479;
RP PRO-978 AND LYS-1125, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24594635; DOI=10.1136/gutjnl-2014-306896;
RA Gordo-Gilart R., Andueza S., Hierro L., Martinez-Fernandez P.,
RA D'Agostino D., Jara P., Alvarez L.;
RT "Functional analysis of ABCB4 mutations relates clinical outcomes of
RT progressive familial intrahepatic cholestasis type 3 to the degree of MDR3
RT floppase activity.";
RL Gut 64:147-155(2015).
RN [38]
RP CHARACTERIZATION OF VARIANTS GBD1 ARG-536; LEU-726; LEU-1183 AND SER-1185,
RP CHARACTERIZATION OF VARIANT PFIC3 ASP-535, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=28012258; DOI=10.1002/hep.28929;
RA Delaunay J.L., Bruneau A., Hoffmann B., Durand-Schneider A.M., Barbu V.,
RA Jacquemin E., Maurice M., Housset C., Callebaut I., Ait-Slimane T.;
RT "Functional defect of variants in the adenosine triphosphate-binding sites
RT of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance
RT regulator potentiator, ivacaftor (VX-770).";
RL Hepatology 65:560-570(2017).
RN [39]
RP CHARACTERIZATION OF VARIANTS GBD1 ASP-528 AND SER-1168.
RX PubMed=28587926; DOI=10.1016/j.biocel.2017.05.028;
RA Khabou B., Durand-Schneider A.M., Delaunay J.L., Ait-Slimane T., Barbu V.,
RA Fakhfakh F., Housset C., Maurice M.;
RT "Comparison of in silico prediction and experimental assessment of ABCB4
RT variants identified in patients with biliary diseases.";
RL Int. J. Biochem. Cell Biol. 89:101-109(2017).
CC -!- FUNCTION: [Isoform 1]: Energy-dependent phospholipid efflux
CC translocator that acts as a positive regulator of biliary lipid
CC secretion. Functions as a floppase that translocates specifically
CC phosphatidylcholine (PC) from the inner to the outer leaflet of the
CC canalicular membrane bilayer into the canaliculi of hepatocytes.
CC Translocation of PC makes the biliary phospholipids available for
CC extraction into the canaliculi lumen by bile salt mixed micelles and
CC therefore protects the biliary tree from the detergent activity of bile
CC salts (PubMed:7957936, PubMed:8898203, PubMed:9366571, PubMed:17523162,
CC PubMed:23468132, PubMed:24806754, PubMed:24723470, PubMed:24594635,
CC PubMed:21820390, PubMed:31873305). Plays a role in the recruitment of
CC phosphatidylcholine (PC), phosphatidylethanolamine (PE) and
CC sphingomyelin (SM) molecules to nonraft membranes and to further
CC enrichment of SM and cholesterol in raft membranes in hepatocytes
CC (PubMed:23468132). Required for proper phospholipid bile formation (By
CC similarity). Indirectly involved in cholesterol efflux activity from
CC hepatocytes into the canalicular lumen in the presence of bile salts in
CC an ATP-dependent manner (PubMed:24045840). Promotes biliary
CC phospholipid secretion as canaliculi-containing vesicles from the
CC canalicular plasma membrane (PubMed:9366571, PubMed:28012258). In
CC cooperation with ATP8B1, functions to protect hepatocytes from the
CC deleterious detergent activity of bile salts (PubMed:21820390). Does
CC not confer multidrug resistance (By similarity).
CC {ECO:0000250|UniProtKB:P21440, ECO:0000269|PubMed:17523162,
CC ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:23468132,
CC ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635,
CC ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:24806754,
CC ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:31873305,
CC ECO:0000269|PubMed:7957936, ECO:0000269|PubMed:8898203,
CC 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:0000250|UniProtKB:P21440};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
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:31873305};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66273;
CC Evidence={ECO:0000269|PubMed:31873305};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
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:0000250|UniProtKB:P21440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66273;
CC Evidence={ECO:0000250|UniProtKB:P21440};
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:0000269|PubMed:8898203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36440;
CC Evidence={ECO:0000305|PubMed:8898203};
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:0000269|PubMed:8898203};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38904;
CC Evidence={ECO:0000305|PubMed:8898203};
CC -!- ACTIVITY REGULATION: Translocation activity is inhibited by the ATPase
CC inhibitor vanadate and the calcium channel blocker verapamil
CC (PubMed:17523162, PubMed:23468132). Translocation activity is enhanced
CC by the addition of the bile salt taurocholate (PubMed:17523162,
CC PubMed:23468132). {ECO:0000269|PubMed:17523162,
CC ECO:0000269|PubMed:23468132}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.6 mM for ATP {ECO:0000269|PubMed:31873305};
CC Vmax=80 nmol/min/mg enzyme toward ATP {ECO:0000269|PubMed:31873305};
CC -!- SUBUNIT: May interact with RACK1 (PubMed:19674157). Interacts with HAX1
CC (By similarity). {ECO:0000250|UniProtKB:Q08201,
CC ECO:0000269|PubMed:19674157}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23468132,
CC ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24806754,
CC ECO:0000269|PubMed:28012258}; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441}. Apical cell membrane
CC {ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:19674157,
CC ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:24122873,
CC ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24723470,
CC ECO:0000269|PubMed:8898203}; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441}. Membrane raft
CC {ECO:0000269|PubMed:23468132}. Cytoplasm {ECO:0000269|PubMed:24045840}.
CC Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:Q08201}. Note=Localized at the apical
CC canalicular membrane of the epithelial cells lining the lumen of the
CC bile canaliculi and biliary ductules (By similarity). Transported from
CC the Golgi to the apical bile canalicular membrane in a RACK1-dependent
CC manner (PubMed:19674157). Redistributed into pseudocanaliculi formed
CC between cells in a bezafibrate- or PPARA-dependent manner
CC (PubMed:15258199). Localized preferentially in lipid nonraft domains of
CC canalicular plasma membranes (PubMed:23468132).
CC {ECO:0000250|UniProtKB:P21440, ECO:0000269|PubMed:15258199,
CC ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:23468132}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P21439-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21439-2; Sequence=VSP_023263;
CC Name=3;
CC IsoId=P21439-3; Sequence=VSP_046258, VSP_023263;
CC -!- INDUCTION: Up-regulated by PPARA (PubMed:24122873). Up-regulated by
CC compounds that cause peroxisome proliferation, such as fenofibrate (at
CC protein level). Up-regulated by bezafibrate (PubMed:15258199). Up-
CC regulated by compounds that cause peroxisome proliferation, such as
CC fenofibrate, bezafibrate and gemfibrozil (PubMed:24122873).
CC {ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:24122873}.
CC -!- PTM: Phosphorylated (PubMed:24723470). Phosphorylation on Thr-34 is
CC required for PC efflux activity. Phosphorylation occurs on serine and
CC threonine residues in a protein kinase A- or C-dependent manner
CC (PubMed:24723470). May be phosphorylated on Thr-44 and Ser-49
CC (PubMed:24723470). {ECO:0000269|PubMed:24723470}.
CC -!- PTM: Glycosylated (PubMed:17523162, PubMed:24723470, PubMed:21820390).
CC {ECO:0000269|PubMed:17523162, ECO:0000269|PubMed:21820390,
CC ECO:0000269|PubMed:24723470}.
CC -!- DISEASE: Cholestasis, progressive familial intrahepatic, 3 (PFIC3)
CC [MIM:602347]: A disorder characterized by early onset of cholestasis
CC that progresses to hepatic fibrosis, cirrhosis, and end-stage liver
CC disease before adulthood. PFIC3 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11313315, ECO:0000269|PubMed:12671900,
CC ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:21119540,
CC ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635,
CC ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258,
CC ECO:0000269|PubMed:9419367}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cholestasis of pregnancy, intrahepatic 3 (ICP3) [MIM:614972]:
CC A liver disorder of pregnancy. It presents during the second or, more
CC commonly, the third trimester of pregnancy with intense pruritus which
CC becomes more severe with advancing gestation and cholestasis. It causes
CC fetal distress, spontaneous premature delivery and intrauterine death.
CC Patients have spontaneous and progressive disappearance of cholestasis
CC after delivery. Cholestasis results from abnormal biliary transport
CC from the liver into the small intestine. {ECO:0000269|PubMed:10767346,
CC ECO:0000269|PubMed:12746424, ECO:0000269|PubMed:15077010}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Gallbladder disease 1 (GBD1) [MIM:600803]: One of the major
CC digestive diseases. Gallstones composed of cholesterol (cholelithiasis)
CC are the common manifestations in western countries. Most people with
CC gallstones, however, remain asymptomatic through their lifetimes.
CC {ECO:0000269|PubMed:11313316, ECO:0000269|PubMed:12891548,
CC ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021,
CC ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:28012258,
CC ECO:0000269|PubMed:28587926, ECO:0000269|Ref.2}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA84542.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/abcb4/";
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; M23234; AAA36207.1; -; mRNA.
DR EMBL; EF034088; ABJ53424.1; -; Genomic_DNA.
DR EMBL; AC005045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005068; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236949; EAL24174.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24175.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24176.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76946.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76947.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76948.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76950.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76951.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76952.1; -; Genomic_DNA.
DR EMBL; Z35284; CAA84542.1; ALT_SEQ; mRNA.
DR EMBL; X06181; CAA29547.1; -; mRNA.
DR CCDS; CCDS5605.1; -. [P21439-2]
DR CCDS; CCDS5606.1; -. [P21439-1]
DR CCDS; CCDS5607.1; -. [P21439-3]
DR PIR; JS0051; DVHU3.
DR RefSeq; NP_000434.1; NM_000443.3. [P21439-2]
DR RefSeq; NP_061337.1; NM_018849.2. [P21439-1]
DR RefSeq; NP_061338.1; NM_018850.2. [P21439-3]
DR RefSeq; XP_011514615.1; XM_011516313.2.
DR PDB; 6S7P; EM; 3.20 A; A=1-1286.
DR PDB; 7NIU; EM; 4.20 A; A=1-1286.
DR PDB; 7NIV; EM; 3.60 A; A=1-1286.
DR PDB; 7NIW; EM; 3.80 A; A=1-1286.
DR PDBsum; 6S7P; -.
DR PDBsum; 7NIU; -.
DR PDBsum; 7NIV; -.
DR PDBsum; 7NIW; -.
DR AlphaFoldDB; P21439; -.
DR SMR; P21439; -.
DR BioGRID; 111263; 3.
DR IntAct; P21439; 3.
DR STRING; 9606.ENSP00000265723; -.
DR ChEMBL; CHEMBL1743129; -.
DR DrugBank; DB06414; Etravirine.
DR DrugBank; DB06207; Silodosin.
DR SwissLipids; SLP:000000384; -.
DR TCDB; 3.A.1.201.3; the atp-binding cassette (abc) superfamily.
DR GlyGen; P21439; 2 sites.
DR iPTMnet; P21439; -.
DR PhosphoSitePlus; P21439; -.
DR BioMuta; ABCB4; -.
DR DMDM; 126302568; -.
DR jPOST; P21439; -.
DR MassIVE; P21439; -.
DR MaxQB; P21439; -.
DR PaxDb; P21439; -.
DR PeptideAtlas; P21439; -.
DR PRIDE; P21439; -.
DR ProteomicsDB; 53868; -. [P21439-1]
DR ProteomicsDB; 53869; -. [P21439-2]
DR ProteomicsDB; 613; -.
DR Antibodypedia; 3853; 227 antibodies from 33 providers.
DR DNASU; 5244; -.
DR Ensembl; ENST00000265723.8; ENSP00000265723.4; ENSG00000005471.19. [P21439-1]
DR Ensembl; ENST00000359206.8; ENSP00000352135.3; ENSG00000005471.19. [P21439-2]
DR Ensembl; ENST00000453593.5; ENSP00000392983.1; ENSG00000005471.19. [P21439-3]
DR Ensembl; ENST00000649586.2; ENSP00000496956.2; ENSG00000005471.19. [P21439-2]
DR GeneID; 5244; -.
DR KEGG; hsa:5244; -.
DR MANE-Select; ENST00000649586.2; ENSP00000496956.2; NM_000443.4; NP_000434.1. [P21439-2]
DR UCSC; uc003uiv.2; human. [P21439-1]
DR CTD; 5244; -.
DR DisGeNET; 5244; -.
DR GeneCards; ABCB4; -.
DR HGNC; HGNC:45; ABCB4.
DR HPA; ENSG00000005471; Tissue enriched (liver).
DR MalaCards; ABCB4; -.
DR MIM; 171060; gene.
DR MIM; 600803; phenotype.
DR MIM; 602347; phenotype.
DR MIM; 614972; phenotype.
DR neXtProt; NX_P21439; -.
DR OpenTargets; ENSG00000005471; -.
DR Orphanet; 69665; Intrahepatic cholestasis of pregnancy.
DR Orphanet; 69663; Low phospholipid-associated cholelithiasis.
DR Orphanet; 79305; Progressive familial intrahepatic cholestasis type 3.
DR PharmGKB; PA268; -.
DR VEuPathDB; HostDB:ENSG00000005471; -.
DR eggNOG; KOG0055; Eukaryota.
DR GeneTree; ENSGT00940000159418; -.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; P21439; -.
DR OMA; YIYLNYG; -.
DR OrthoDB; 186078at2759; -.
DR PhylomeDB; P21439; -.
DR TreeFam; TF105193; -.
DR PathwayCommons; P21439; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-5678771; Defective ABCB4 causes PFIC3, ICP3 and GBD1.
DR SignaLink; P21439; -.
DR SIGNOR; P21439; -.
DR BioGRID-ORCS; 5244; 10 hits in 1069 CRISPR screens.
DR ChiTaRS; ABCB4; human.
DR GeneWiki; ABCB4; -.
DR GenomeRNAi; 5244; -.
DR Pharos; P21439; Tbio.
DR PRO; PR:P21439; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P21439; protein.
DR Bgee; ENSG00000005471; Expressed in right lobe of liver and 116 other tissues.
DR ExpressionAtlas; P21439; baseline and differential.
DR Genevisible; P21439; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IDA:UniProtKB.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IDA:UniProtKB.
DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IBA:GO_Central.
DR GO; GO:0005548; F:phospholipid transporter activity; TAS:Reactome.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:1903413; P:cellular response to bile acid; IDA:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0045332; P:phospholipid translocation; IDA:BHF-UCL.
DR GO; GO:0032376; P:positive regulation of cholesterol transport; IDA:UniProtKB.
DR GO; GO:0061092; P:positive regulation of phospholipid translocation; IDA:UniProtKB.
DR GO; GO:2001140; P:positive regulation of phospholipid transport; IDA:UniProtKB.
DR GO; GO:1901557; P:response to fenofibrate; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
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 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Disease variant; Glycoprotein;
KW Intrahepatic cholestasis; Lipid transport; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1286
FT /note="Phosphatidylcholine translocator ABCB4"
FT /id="PRO_0000093333"
FT TOPO_DOM 1..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 51..73
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 74..118
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 140..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 189..210
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 211..217
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 239..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 297..318
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 319..332
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 333..354
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 355..711
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 712..732
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 733..755
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 756..776
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 777..831
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 832..852
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 853
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 854..873
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 874..933
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 934..956
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 957..972
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 973..994
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 995..1286
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 57..359
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 394..630
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 711..999
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1034..1279
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 625..647
FT /note="Interaction with HAX1"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:31873305,
FT ECO:0007744|PDB:6S7P"
FT BINDING 432..437
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:31873305, ECO:0007744|PDB:6S7P"
FT BINDING 477
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:31873305,
FT ECO:0007744|PDB:6S7P"
FT BINDING 536
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:31873305,
FT ECO:0007744|PDB:6S7P"
FT BINDING 1046
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:31873305,
FT ECO:0007744|PDB:6S7P"
FT BINDING 1071..1077
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:31873305, ECO:0007744|PDB:6S7P"
FT BINDING 1124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:31873305,
FT ECO:0007744|PDB:6S7P"
FT BINDING 1184..1186
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:31873305, ECO:0007744|PDB:6S7P"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21440"
FT MOD_RES 34
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:24723470"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 929..975
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046258"
FT VAR_SEQ 1094..1100
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:2906314"
FT /id="VSP_023263"
FT VARIANT 34
FT /note="T -> M (in GBD1; reduces efflux activity for PC in a
FT phosphorylation-dependent manner; dbSNP:rs142794414)"
FT /evidence="ECO:0000269|PubMed:22331132,
FT ECO:0000269|PubMed:24723470"
FT /id="VAR_073728"
FT VARIANT 47
FT /note="R -> G (in GBD1; partly retained intracellularly;
FT reduces efflux activity for PC in a phosphorylation-
FT dependent manner)"
FT /evidence="ECO:0000269|PubMed:22331132,
FT ECO:0000269|PubMed:23533021, ECO:0000269|PubMed:24723470"
FT /id="VAR_073729"
FT VARIANT 47
FT /note="R -> Q (found in patients with cholangitis; unknown
FT pathological significance; dbSNP:rs372685632)"
FT /evidence="ECO:0000269|PubMed:22331132"
FT /id="VAR_073730"
FT VARIANT 68
FT /note="G -> R (in PFIC3; retained in the reticulum
FT endoplasmic; greatly reduced expression;
FT dbSNP:rs1343667900)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073731"
FT VARIANT 70
FT /note="G -> R (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:21119540"
FT /id="VAR_073732"
FT VARIANT 71
FT /note="L -> H (in GBD1; dbSNP:rs780641693)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073733"
FT VARIANT 73
FT /note="L -> V (in PFIC3 and GBD1; dbSNP:rs8187788)"
FT /evidence="ECO:0000269|PubMed:21119540,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_073734"
FT VARIANT 78
FT /note="F -> C (in GBD1; dbSNP:rs1411970557)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073735"
FT VARIANT 87
FT /note="D -> E"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_043078"
FT VARIANT 95
FT /note="P -> S (in dbSNP:rs377268767)"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_043079"
FT VARIANT 99
FT /note="S -> F (in GBD1; dbSNP:rs1408217402)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073736"
FT VARIANT 124
FT /note="G -> S (in GBD1)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073737"
FT VARIANT 126
FT /note="G -> E (in PFIC3; dbSNP:rs1021988376)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073738"
FT VARIANT 138
FT /note="W -> R (in PFIC3; dbSNP:rs72552781)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043080"
FT VARIANT 150
FT /note="R -> K (in ICP3; dbSNP:rs757693457)"
FT /evidence="ECO:0000269|PubMed:12746424"
FT /id="VAR_043081"
FT VARIANT 154
FT /note="F -> S (in GBD1)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073739"
FT VARIANT 165
FT /note="F -> I (in GBD1)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_043082"
FT VARIANT 175
FT /note="T -> A (found in patients with gallbladder and
FT cholestasis; unknown pathological significance;
FT dbSNP:rs58238559)"
FT /evidence="ECO:0000269|PubMed:11313316,
FT ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:15077010,
FT ECO:0000269|PubMed:16763017, ECO:0000269|PubMed:17264802,
FT ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:22331132,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_023501"
FT VARIANT 201
FT /note="T -> M (in PFIC3; greatly reduced expression; alters
FT efflux activity for PC; dbSNP:rs753318087)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073740"
FT VARIANT 238
FT /note="L -> V (in dbSNP:rs45596335)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020223"
FT VARIANT 250
FT /note="A -> P (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073741"
FT VARIANT 263
FT /note="I -> V (in dbSNP:rs45547936)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_030763"
FT VARIANT 286
FT /note="A -> V (in PFIC3 and GBD1; does not alter plasma
FT membrane location; inhibits efflux activity for PC;
FT dbSNP:rs765478923)"
FT /evidence="ECO:0000269|PubMed:17726488,
FT ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021,
FT ECO:0000269|PubMed:24806754"
FT /id="VAR_073742"
FT VARIANT 301
FT /note="M -> T (in GBD1; dbSNP:rs72552779)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_043083"
FT VARIANT 320
FT /note="S -> F (in ICP3, GBD1 and PFIC3; unknown
FT pathological significance; does not alter plasma membrane
FT location; does not inhibit efflux activity for PC;
FT dbSNP:rs72552778)"
FT /evidence="ECO:0000269|PubMed:11313316,
FT ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:15077010,
FT ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:21119540,
FT ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021,
FT ECO:0000269|PubMed:24806754"
FT /id="VAR_023502"
FT VARIANT 346
FT /note="S -> I (in PFIC3; dbSNP:rs67876345)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043084"
FT VARIANT 357
FT /note="F -> L (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073743"
FT VARIANT 364
FT /note="A -> V (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073744"
FT VARIANT 367
FT /note="I -> V (in dbSNP:rs1168923653)"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_043085"
FT VARIANT 395
FT /note="E -> G (in PFIC3; dbSNP:rs72552777)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043086"
FT VARIANT 403
FT /note="Y -> H (in PFIC3; does not alter cytoplasmic and
FT cell membrane location; inhibits efflux activity for PC and
FT cholesterol; dbSNP:rs121918443)"
FT /evidence="ECO:0000269|PubMed:17726488,
FT ECO:0000269|PubMed:21119540, ECO:0000269|PubMed:24045840"
FT /id="VAR_073745"
FT VARIANT 406
FT /note="R -> G (in GBD1)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073746"
FT VARIANT 406
FT /note="R -> Q (found in patients with cholangitis; unknown
FT pathological significance; dbSNP:rs763807769)"
FT /evidence="ECO:0000269|PubMed:22331132"
FT /id="VAR_073747"
FT VARIANT 424
FT /note="T -> A (in PFIC3; dbSNP:rs1263565476)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043087"
FT VARIANT 425
FT /note="V -> M (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043088"
FT VARIANT 450
FT /note="E -> G (in dbSNP:rs1189003716)"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_043089"
FT VARIANT 459
FT /note="D -> H (in PFIC3; retained in the reticulum
FT endoplasmic; greatly reduced expression)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073748"
FT VARIANT 475
FT /note="V -> A (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073749"
FT VARIANT 479
FT /note="P -> L (in PFIC3; greatly reduced expression; alters
FT efflux activity for PC; dbSNP:rs748657435)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073750"
FT VARIANT 481
FT /note="L -> R (in PFIC3; does not alter cytoplasmic and
FT cell membrane location; inhibits efflux activity for PC and
FT cholesterol)"
FT /evidence="ECO:0000269|PubMed:24045840"
FT /id="VAR_073751"
FT VARIANT 510
FT /note="N -> S (in GBD1; dbSNP:rs375315619)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073752"
FT VARIANT 511
FT /note="A -> T (in PFIC3 and GBD1; dbSNP:rs1257887155)"
FT /evidence="ECO:0000269|PubMed:17726488,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_073753"
FT VARIANT 513
FT /note="E -> K (in GBD1)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073754"
FT VARIANT 528
FT /note="E -> D (in GBD1; unknown pathological significance;
FT moderate decrease of phosphatidylcholine transporter
FT activity; does not alter plasma membrane location;
FT dbSNP:rs8187797)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:15077010, ECO:0000269|PubMed:22331132,
FT ECO:0000269|PubMed:23533021, ECO:0000269|PubMed:28587926,
FT ECO:0000269|Ref.2"
FT /id="VAR_043090"
FT VARIANT 535
FT /note="G -> D (in PFIC3; reduced phosphatidylcholine
FT transporter activity; does not alter plasma membrane
FT location)"
FT /evidence="ECO:0000269|PubMed:12671900,
FT ECO:0000269|PubMed:28012258"
FT /id="VAR_043091"
FT VARIANT 536
FT /note="G -> R (in GBD1; loss of phosphatidylcholine
FT transporter activity; does not alter plasma membrane
FT location)"
FT /evidence="ECO:0000269|PubMed:28012258"
FT /id="VAR_079611"
FT VARIANT 541
FT /note="I -> F (in PFIC3 and GBD1; dbSNP:rs66904256)"
FT /evidence="ECO:0000269|PubMed:11313315,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_043092"
FT VARIANT 545
FT /note="R -> H (in GBD1)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073755"
FT VARIANT 546
FT /note="A -> D (in ICP3; disruption of protein trafficking
FT with subsequent lack of functional protein at the cell
FT surface; dbSNP:rs121918441)"
FT /evidence="ECO:0000269|PubMed:10767346"
FT /id="VAR_023503"
FT VARIANT 549
FT /note="R -> H (in GBD1; dbSNP:rs761238221)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073756"
FT VARIANT 556
FT /note="L -> R (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043093"
FT VARIANT 558
FT /note="E -> K (in PFIC3; dbSNP:rs1562975478)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073757"
FT VARIANT 564
FT /note="D -> G (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043094"
FT VARIANT 589
FT /note="H -> T (in GBD1; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073758"
FT VARIANT 590
FT /note="R -> Q (found in patients with gallbladder and
FT cholestasis; unknown pathological significance;
FT dbSNP:rs45575636)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:16763017, ECO:0000269|PubMed:17264802,
FT ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:19261551,
FT ECO:0000269|PubMed:23533021, ECO:0000269|Ref.2"
FT /id="VAR_043095"
FT VARIANT 591
FT /note="L -> Q (in GBD1; dbSNP:rs72552776)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_043096"
FT VARIANT 593
FT /note="T -> A (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073759"
FT VARIANT 593
FT /note="T -> M (in GBD1; dbSNP:rs571555115)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073760"
FT VARIANT 630
FT /note="M -> V (in PFIC3; dbSNP:rs372476723)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073761"
FT VARIANT 647
FT /note="E -> K (in GBD1; dbSNP:rs972726699)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073762"
FT VARIANT 651
FT /note="T -> N (in dbSNP:rs45476795)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_030765"
FT VARIANT 652
FT /note="R -> G (in dbSNP:rs2230028)"
FT /evidence="ECO:0000269|PubMed:11313315,
FT ECO:0000269|PubMed:12746424, ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:15077010, ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:17264802, ECO:0000269|PubMed:19261551,
FT ECO:0000269|PubMed:21119540, ECO:0000269|Ref.2"
FT /id="VAR_020225"
FT VARIANT 701
FT /note="L -> P (in PFIC3; dbSNP:rs988987669)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073763"
FT VARIANT 711
FT /note="F -> S (in PFIC3; dbSNP:rs72552773)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043097"
FT VARIANT 715
FT /note="T -> I (in PFIC3; dbSNP:rs138773456)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073764"
FT VARIANT 723
FT /note="G -> E (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073765"
FT VARIANT 726
FT /note="P -> L (in GBD1; loss of phosphatidylcholine
FT transporter activity; does not alter plasma membrane
FT location; dbSNP:rs141677867)"
FT /evidence="ECO:0000269|PubMed:23533021,
FT ECO:0000269|PubMed:28012258"
FT /id="VAR_073766"
FT VARIANT 726
FT /note="P -> T (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073767"
FT VARIANT 729
FT /note="S -> L (in GBD1; dbSNP:rs970324585)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073768"
FT VARIANT 737
FT /note="A -> V (in PFIC3; dbSNP:rs147134978)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073769"
FT VARIANT 742
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:12891548"
FT /id="VAR_043098"
FT VARIANT 762
FT /note="G -> E (in ICP3)"
FT /evidence="ECO:0000269|PubMed:15077010"
FT /id="VAR_043099"
FT VARIANT 764
FT /note="I -> L (in a heterozygous patient with risperidone-
FT induced cholestasis)"
FT /evidence="ECO:0000269|PubMed:17264802"
FT /id="VAR_043100"
FT VARIANT 775
FT /note="T -> M (found in patients with cholangitis; unknown
FT pathological significance; dbSNP:rs148052192)"
FT /evidence="ECO:0000269|PubMed:15077010,
FT ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:22331132"
FT /id="VAR_043101"
FT VARIANT 788
FT /note="R -> Q (in GBD1; benign variant; dbSNP:rs8187801)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:23533021, ECO:0000269|Ref.2"
FT /id="VAR_024359"
FT VARIANT 840
FT /note="A -> D (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073770"
FT VARIANT 934
FT /note="A -> T (found in patients with gallbladder and
FT cholestasis; unknown pathological significance;
FT dbSNP:rs61730509)"
FT /evidence="ECO:0000269|PubMed:12891548,
FT ECO:0000269|PubMed:23533021"
FT /id="VAR_043102"
FT VARIANT 954
FT /note="G -> S (in PFIC3; dbSNP:rs779829759)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073771"
FT VARIANT 964
FT /note="V -> T (requires 2 nucleotide substitutions; found
FT in patients with cholangitis; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:22331132"
FT /id="VAR_073772"
FT VARIANT 975
FT /note="L -> V (in GBD1; dbSNP:rs759787957)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073773"
FT VARIANT 978
FT /note="S -> P (in PFIC3; alters efflux activity for PC;
FT dbSNP:rs1051861187)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073774"
FT VARIANT 983
FT /note="G -> S (in PFIC3; dbSNP:rs56187107)"
FT /evidence="ECO:0000269|PubMed:11313315"
FT /id="VAR_043103"
FT VARIANT 1082
FT /note="L -> Q (in a heterozygous patient with amoxicillin/
FT clavulanic acid-induced cholestasis; dbSNP:rs1214110864)"
FT /evidence="ECO:0000269|PubMed:17264802"
FT /id="VAR_043104"
FT VARIANT 1084
FT /note="R -> W (in GBD1; dbSNP:rs1262922848)"
FT /evidence="ECO:0000269|PubMed:23533021"
FT /id="VAR_073775"
FT VARIANT 1125
FT /note="E -> K (in PFIC3; alters efflux activity for PC)"
FT /evidence="ECO:0000269|PubMed:24594635"
FT /id="VAR_073776"
FT VARIANT 1161
FT /note="Missing (in GBD1)"
FT /id="VAR_043105"
FT VARIANT 1168
FT /note="P -> S (in GBD1; reduced phosphatidylcholine
FT transporter activity; does not alter plasma membrane
FT location; dbSNP:rs121918442)"
FT /evidence="ECO:0000269|PubMed:11313316,
FT ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:28587926"
FT /id="VAR_023504"
FT VARIANT 1183
FT /note="S -> L (in GBD1; severely reduced
FT phosphatidylcholine transporter activity; does not alter
FT plasma membrane location)"
FT /evidence="ECO:0000269|PubMed:28012258"
FT /id="VAR_079612"
FT VARIANT 1185
FT /note="G -> S (in GBD1; loss of phosphatidylcholine
FT transporter activity; does not alter plasma membrane
FT location)"
FT /evidence="ECO:0000269|PubMed:28012258"
FT /id="VAR_079613"
FT VARIANT 1193
FT /note="A -> T (in PFIC3)"
FT /evidence="ECO:0000269|PubMed:17726488"
FT /id="VAR_073777"
FT MUTAGEN 34
FT /note="T->D: Does not inhibit efflux activity for PC."
FT /evidence="ECO:0000269|PubMed:24723470"
FT MUTAGEN 44
FT /note="T->A: Reduces efflux activity for PC. Does not alter
FT apical membrane location."
FT /evidence="ECO:0000269|PubMed:24723470"
FT MUTAGEN 49
FT /note="S->A: Reduces efflux activity for PC. Does not alter
FT apical membrane location."
FT /evidence="ECO:0000269|PubMed:24723470"
FT MUTAGEN 435
FT /note="K->M: Inhibits efflux activity for PC and
FT cholesterol, but does not alter glycosylation and surface
FT expression in the presence of taurocholate."
FT /evidence="ECO:0000269|PubMed:17523162"
FT MUTAGEN 558
FT /note="E->Q: Loss of floppase activity. Strongly reduce the
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:31873305"
FT MUTAGEN 953
FT /note="A->D: Accumulates predominantly in intracellular
FT compartments with only a small fraction at the plasma
FT membrane and inhibits partially the efflux activity for
FT PC."
FT /evidence="ECO:0000269|PubMed:24806754"
FT MUTAGEN 985
FT /note="V->M: Significantly reduces phosphatidylcholine
FT floppase activity; when associated with Q-989 and V-990."
FT /evidence="ECO:0000269|PubMed:31873305"
FT MUTAGEN 989
FT /note="H->Q: Significantly reduces phosphatidylcholine
FT floppase activity; when associated with M-985 and V-990."
FT /evidence="ECO:0000269|PubMed:31873305"
FT MUTAGEN 990
FT /note="A->V: Significantly reduces phosphatidylcholine
FT floppase activity; when associated with M-985 and Q-989."
FT /evidence="ECO:0000269|PubMed:31873305"
FT MUTAGEN 1075
FT /note="K->M: Inhibits efflux activity for PC and
FT cholesterol, but does not alter glycosylation and surface
FT expression in the presence of taurocholate."
FT /evidence="ECO:0000269|PubMed:17523162"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 51..68
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 108..159
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 162..167
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 173..187
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 190..212
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 214..221
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 224..261
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 272..324
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 330..349
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 351..372
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 394..398
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 424..428
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 435..442
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 465..471
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 472..475
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 486..494
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 499..508
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 512..517
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 535..547
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 552..558
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 565..578
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 583..587
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 598..604
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 607..612
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 614..618
FT /evidence="ECO:0007829|PDB:6S7P"
FT TURN 619..621
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 623..628
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 697..700
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 708..722
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 724..738
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 739..742
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 744..746
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 747..795
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 800..804
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 810..828
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 831..852
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 854..860
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 861..863
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 864..901
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 903..909
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 912..965
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 970..1012
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1034..1038
FT /evidence="ECO:0007829|PDB:6S7P"
FT TURN 1045..1048
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1051..1053
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1056..1059
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1064..1068
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1075..1083
FT /evidence="ECO:0007829|PDB:6S7P"
FT TURN 1107..1109
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1112..1117
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1119..1122
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1130..1132
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1133..1138
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1148..1157
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1161..1166
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1167..1171
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1177..1179
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1184..1196
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1201..1207
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1209..1212
FT /evidence="ECO:0007829|PDB:6S7P"
FT HELIX 1214..1227
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1231..1236
FT /evidence="ECO:0007829|PDB:6S7P"
FT TURN 1240..1245
FT /evidence="ECO:0007829|PDB:6S7P"
FT STRAND 1247..1253
FT /evidence="ECO:0007829|PDB:6S7P"
SQ SEQUENCE 1286 AA; 141523 MW; 9A9066F2292F2CCF CRC64;
MDLEAAKNGT AWRPTSAEGD FELGISSKQK RKKTKTVKMI GVLTLFRYSD WQDKLFMSLG
TIMAIAHGSG LPLMMIVFGE MTDKFVDTAG NFSFPVNFSL SLLNPGKILE EEMTRYAYYY
SGLGAGVLVA AYIQVSFWTL AAGRQIRKIR QKFFHAILRQ EIGWFDINDT TELNTRLTDD
ISKISEGIGD KVGMFFQAVA TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILSA
FSDKELAAYA KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKEIG IKKAISANIS
MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA APCIDAFANA
RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLEFNDVH FSYPSRANVK ILKGLNLKVQ
SGQTVALVGS SGCGKSTTVQ LIQRLYDPDE GTINIDGQDI RNFNVNYLRE IIGVVSQEPV
LFSTTIAENI CYGRGNVTMD EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR
IAIARALVRN PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI
AGFEDGVIVE QGSHSELMKK EGVYFKLVNM QTSGSQIQSE EFELNDEKAA TRMAPNGWKS
RLFRHSTQKN LKNSQMCQKS LDVETDGLEA NVPPVSFLKV LKLNKTEWPY FVVGTVCAIA
NGGLQPAFSV IFSEIIAIFG PGDDAVKQQK CNIFSLIFLF LGIISFFTFF LQGFTFGKAG
EILTRRLRSM AFKAMLRQDM SWFDDHKNST GALSTRLATD AAQVQGATGT RLALIAQNIA
NLGTGIIISF IYGWQLTLLL LAVVPIIAVS GIVEMKLLAG NAKRDKKELE AAGKIATEAI
ENIRTVVSLT QERKFESMYV EKLYGPYRNS VQKAHIYGIT FSISQAFMYF SYAGCFRFGA
YLIVNGHMRF RDVILVFSAI VFGAVALGHA SSFAPDYAKA KLSAAHLFML FERQPLIDSY
SEEGLKPDKF EGNITFNEVV FNYPTRANVP VLQGLSLEVK KGQTLALVGS SGCGKSTVVQ
LLERFYDPLA GTVFVDFGFQ LLDGQEAKKL NVQWLRAQLG IVSQEPILFD CSIAENIAYG
DNSRVVSQDE IVSAAKAANI HPFIETLPHK YETRVGDKGT QLSGGQKQRI AIARALIRQP
QILLLDEATS ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VFQNGRVKEH
GTHQQLLAQK GIYFSMVSVQ AGTQNL
