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 22-FEB-2023, entry version 218. 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; DOI=10.1002/j.1460-2075.1987.tb02653.x; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P21439; 2 sites, No reported glycans. 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 ProteomicsDB; 53868; -. [P21439-1] DR ProteomicsDB; 53869; -. [P21439-2] DR ProteomicsDB; 613; -. DR Antibodypedia; 3853; 233 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 AGR; HGNC:45; -. 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; 5487044at2759; -. 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 1156 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:0046581; C:intercellular canaliculus; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IBA:GO_Central. 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:0016887; F:ATP hydrolysis activity; IEA:InterPro. 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 CDD; cd18578; ABC_6TM_Pgp_ABCB1_D2_like; 1. DR CDD; cd03249; ABC_MTABC3_MDL1_MDL2; 2. DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; IPR027417; P-loop_NTPase. DR InterPro; IPR039421; Type_1_exporter. DR PANTHER; PTHR24222; ABC TRANSPORTER B FAMILY; 1. DR PANTHER; PTHR24222:SF76; MYCOBACTIN IMPORT ATP-BINDING/PERMEASE PROTEIN IRTB; 1. DR Pfam; PF00664; ABC_membrane; 2. DR Pfam; PF00005; ABC_tran; 2. DR SMART; SM00382; AAA; 2. DR SUPFAM; SSF90123; ABC transporter transmembrane region; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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 //