ABCBB_HUMAN
ID ABCBB_HUMAN Reviewed; 1321 AA.
AC O95342; Q53TL2; Q9UNB2;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Bile salt export pump {ECO:0000303|Ref.2};
DE EC=7.6.2.- {ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:16332456, ECO:0000269|PubMed:22262466};
DE AltName: Full=ATP-binding cassette sub-family B member 11;
GN Name=ABCB11 {ECO:0000312|HGNC:HGNC:42}; Synonyms=BSEP {ECO:0000303|Ref.2};
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], AND VARIANTS PFIC2 GLY-297; GLU-461; GLY-482;
RP ARG-982; CYS-1153 AND GLN-1268.
RX PubMed=9806540; DOI=10.1038/3034;
RA Strautnieks S.S., Bull L.N., Knisely A.S., Kocoshis S.A., Dahl N.,
RA Arnell H., Sokal E.M., Dahan K., Childs S., Ling V., Tanner M.S.,
RA Kagalwalla A.F., Nemeth A., Pawlowska J., Baker A., Mieli-Vergani G.,
RA Freimer N.B., Gardiner R.M., Thompson R.J.;
RT "A gene encoding a liver-specific ABC transporter is mutated in progressive
RT familial intrahepatic cholestasis.";
RL Nat. Genet. 20:233-238(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-444.
RA Mol O., Hooiveld G.J.E.J., Jansen P.L.M., Muller M.;
RT "Cellular localization and functional characterization of the human bile
RT salt export pump (BSEP).";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND ACTIVITY
RP REGULATION.
RX PubMed=16332456; DOI=10.1016/j.bbalip.2005.10.006;
RA Hayashi H., Takada T., Suzuki H., Onuki R., Hofmann A.F., Sugiyama Y.;
RT "Transport by vesicles of glycine- and taurine-conjugated bile salts and
RT taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep.";
RL Biochim. Biophys. Acta 1738:54-62(2005).
RN [5]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=15901796; DOI=10.1124/jpet.105.084830;
RA Hirano M., Maeda K., Hayashi H., Kusuhara H., Sugiyama Y.;
RT "Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid
RT substrate, pravastatin.";
RL J. Pharmacol. Exp. Ther. 314:876-882(2005).
RN [6]
RP GLYCOSYLATION AT ASN-109; ASN-116; ASN-122 AND ASN-125.
RX PubMed=17082223; DOI=10.1152/ajpgi.00415.2006;
RA Mochizuki K., Kagawa T., Numari A., Harris M.J., Itoh J., Watanabe N.,
RA Mine T., Arias I.M.;
RT "Two N-linked glycans are required to maintain the transport activity of
RT the bile salt export pump (ABCB11) in MDCK II cells.";
RL Am. J. Physiol. 292:G818-G828(2007).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RC TISSUE=Liver;
RX PubMed=18985798; DOI=10.1002/bdd.629;
RA Yabuuchi H., Tanaka K., Maeda M., Takemura M., Oka M., Ohashi R., Tamai I.;
RT "Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional
RT comparison with the human and rat proteins.";
RL Biopharm. Drug Dispos. 29:441-448(2008).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18245269; DOI=10.1124/mol.107.041459;
RA Matsushima S., Maeda K., Hayashi H., Debori Y., Schinkel A.H.,
RA Schuetz J.D., Kusuhara H., Sugiyama Y.;
RT "Involvement of multiple efflux transporters in hepatic disposition of
RT fexofenadine.";
RL Mol. Pharmacol. 73:1474-1483(2008).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=19228692; DOI=10.1074/jbc.m808667200;
RA Paulusma C.C., de Waart D.R., Kunne C., Mok K.S., Elferink R.P.;
RT "Activity of the bile salt export pump (ABCB11) is critically dependent on
RT canalicular membrane cholesterol content.";
RL J. Biol. Chem. 284:9947-9954(2009).
RN [10]
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RX PubMed=20398791; DOI=10.1016/j.bbalip.2010.04.002;
RA Kato T., Hayashi H., Sugiyama Y.;
RT "Short- and medium-chain fatty acids enhance the cell surface expression
RT and transport capacity of the bile salt export pump (BSEP/ABCB11).";
RL Biochim. Biophys. Acta 1801:1005-1012(2010).
RN [11]
RP SUBCELLULAR LOCATION, INTERACTION WITH AP2A2 AND AP2A1, FUNCTION, CATALYTIC
RP ACTIVITY, REGION, AND MUTAGENESIS OF TYR-1311.
RX PubMed=22262466; DOI=10.1002/hep.25591;
RA Hayashi H., Inamura K., Aida K., Naoi S., Horikawa R., Nagasaka H.,
RA Takatani T., Fukushima T., Hattori A., Yabuki T., Horii I., Sugiyama Y.;
RT "AP2 adaptor complex mediates bile salt export pump internalization and
RT modulates its hepatocanalicular expression and transport function.";
RL Hepatology 55:1889-1900(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-586; SER-587; SER-704 AND
RP SER-1214, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13] {ECO:0007744|PDB:6LR0}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS), CATALYTIC ACTIVITY,
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 1-MET--LEU-441.
RX PubMed=32203132; DOI=10.1038/s41422-020-0302-0;
RA Wang L., Hou W.T., Chen L., Jiang Y.L., Xu D., Sun L., Zhou C.Z., Chen Y.;
RT "Cryo-EM structure of human bile salts exporter ABCB11.";
RL Cell Res. 30:623-625(2020).
RN [14]
RP VARIANTS PFIC2 VAL-238 AND SER-336.
RX PubMed=10579978; DOI=10.1016/s0016-5085(99)70287-8;
RA Jansen P.L.M., Strautnieks S.S., Jacquemin E., Hadchouel M., Sokal E.M.,
RA Hooiveld G.J.E.J., Koning J.H., De Jager-Krikken A., Kuipers F.,
RA Stellaard F., Bijleveld C.M., Gouw A., Van Goor H., Thompson R.J.,
RA Muller M.;
RT "Hepatocanalicular bile salt export pump deficiency in patients with
RT progressive familial intrahepatic cholestasis.";
RL Gastroenterology 117:1370-1379(1999).
RN [15]
RP VARIANT ALA-444.
RX PubMed=11829140; DOI=10.1007/s10038-002-8653-6;
RA Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S.,
RA Nakamura Y.;
RT "Three hundred twenty-six genetic variations in genes encoding nine members
RT of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese
RT population.";
RL J. Hum. Genet. 47:38-50(2002).
RN [16]
RP VARIANTS PFIC2 LEU-284 AND ASP-1004.
RX PubMed=11815775; DOI=10.1067/mpd.2002.119993;
RA Chen H.-L., Chang P.-S., Hsu H.-C., Ni Y.-H., Hsu H.-Y., Lee J.-H.,
RA Jeng Y.-M., Shau W.-Y., Chang M.-H.;
RT "FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic
RT cholestasis with low gamma-glutamyltranspeptidase levels.";
RL J. Pediatr. 140:119-124(2002).
RN [17]
RP VARIANTS BRIC2 GLY-186; GLY-297; THR-570; PRO-923; PRO-926; CYS-1050 AND
RP HIS-1128.
RX PubMed=15300568; DOI=10.1053/j.gastro.2004.04.065;
RA van Mil S.W.C., van der Woerd W.L., van der Brugge G., Sturm E.,
RA Jansen P.L.M., Bull L.N., van den Berg I.E.T., Berger R., Houwen R.H.J.,
RA Klomp L.W.J.;
RT "Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in
RT ABCB11.";
RL Gastroenterology 127:379-384(2004).
RN [18]
RP VARIANTS GLN-415; ALA-444; SER-591 AND VAL-677.
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 [19]
RP CHARACTERIZATION OF VARIANTS PFIC2 GLY-297 AND GLY-482, CATALYTIC ACTIVITY,
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP GLYCOSYLATION.
RX PubMed=15791618; DOI=10.1002/hep.20627;
RA Hayashi H., Takada T., Suzuki H., Akita H., Sugiyama Y.;
RT "Two common PFIC2 mutations are associated with the impaired membrane
RT trafficking of BSEP/ABCB11.";
RL Hepatology 41:916-924(2005).
RN [20]
RP VARIANTS BRIC2 GLY-297 AND THR-432, AND CHARACTERIZATION OF VARIANTS BRIC2
RP GLY-297 AND THR-432.
RX PubMed=16039748; DOI=10.1016/j.jhep.2005.05.020;
RA Noe J., Kullak-Ublick G.A., Jochum W., Stieger B., Kerb R., Haberl M.,
RA Muellhaupt B., Meier P.J., Pauli-Magnus C.;
RT "Impaired expression and function of the bile salt export pump due to three
RT novel ABCB11 mutations in intrahepatic cholestasis.";
RL J. Hepatol. 43:536-543(2005).
RN [21]
RP VARIANTS VAL-206; ALA-284; LYS-299; ALA-444; GLY-616; ALA-619; VAL-677;
RP HIS-698; VAL-865 AND GLN-958.
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 [22]
RP VARIANTS ALA-444 AND VAL-677.
RX PubMed=16799996; DOI=10.1002/hep.21214;
RA Meier Y., Pauli-Magnus C., Zanger U.M., Klein K., Schaeffeler E.,
RA Nussler A.K., Nussler N., Eichelbaum M., Meier P.J., Stieger B.;
RT "Interindividual variability of canalicular ATP-binding-cassette (ABC)-
RT transporter expression in human liver.";
RL Hepatology 44:62-74(2006).
RN [23]
RP VARIANTS ALA-284; ALA-444; TYR-676; VAL-677; HIS-698 AND ARG-855,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF VARIANTS ALA-444;
RP TYR-676; VAL-677 AND ARG-855.
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 [24]
RP CHARACTERIZATION OF VARIANT PFIC2 GLY-297, AND UBIQUITINATION.
RX PubMed=18829893; DOI=10.1124/mol.108.049288;
RA Hayashi H., Sugiyama Y.;
RT "Short-chain ubiquitination is associated with the degradation rate of a
RT cell-surface-resident bile salt export pump (BSEP/ABCB11).";
RL Mol. Pharmacol. 75:143-150(2009).
RN [25]
RP VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND
RP LYS-1186, CHARACTERIZATION OF VARIANTS LEU-56; VAL-206; ALA-444; HIS-558;
RP SER-591; GLN-592; VAL-677 AND LYS-1186, VARIANT PFIC2 GLY-297,
RP CHARACTERIZATION OF VARIANTS PFIC2 GLY-297; ARG-982 AND CYS-1153, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=20010382; DOI=10.1097/fpc.0b013e3283349eb0;
RA Ho R.H., Leake B.F., Kilkenny D.M., Meyer Zu Schwabedissen H.E.,
RA Glaeser H., Kroetz D.L., Kim R.B.;
RT "Polymorphic variants in the human bile salt export pump (BSEP; ABCB11):
RT functional characterization and interindividual variability.";
RL Pharmacogenet. Genomics 20:45-57(2010).
RN [26]
RP VARIANTS PFIC2 HIS-337; CYS-472; TRP-696; PRO-931; VAL-1131 AND ARG-1198,
RP AND VARIANTS ALA-444 AND VAL-865.
RX PubMed=24969679; DOI=10.3892/mmr.2014.2349;
RA Hu G., He P., Liu Z., Chen Q., Zheng B., Zhang Q.;
RT "Diagnosis of ABCB11 gene mutations in children with intrahepatic
RT cholestasis using high resolution melting analysis and direct sequencing.";
RL Mol. Med. Report. 10:1264-1274(2014).
RN [27]
RP CHARACTERIZATION OF VARIANTS BRIC2 GLY-297 AND THR-432, CHARACTERIZATION
RP VARIANT ALA-444, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=24711118; DOI=10.1124/mol.114.092262;
RA Guyot C., Hofstetter L., Stieger B.;
RT "Differential effects of membrane cholesterol content on the transport
RT activity of multidrug resistance-associated protein 2 (ABCC2) and of the
RT bile salt export pump (ABCB11).";
RL Mol. Pharmacol. 85:909-920(2014).
RN [28]
RP VARIANT PFIC2 TYR-129, CHARACTERIZATION OF VARIANT PFIC2 TYR-129,
RP SUBCELLULAR LOCATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29507376; DOI=10.1038/s10038-018-0431-1;
RA Imagawa K., Hayashi H., Sabu Y., Tanikawa K., Fujishiro J., Kajikawa D.,
RA Wada H., Kudo T., Kage M., Kusuhara H., Sumazaki R.;
RT "Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation
RT responsible for progressive infantile cholestasis.";
RL J. Hum. Genet. 63:569-577(2018).
RN [29]
RP VARIANTS LYS-299; ALA-444 AND VAL-865, CHARACTERIZATION OF VARIANT VAL-865,
RP AND SUBCELLULAR LOCATION.
RX PubMed=30431138; DOI=10.3892/mmr.2018.9661;
RA Gan L., Pan S., Cui J., Bai J., Jiang P., He Y.;
RT "Functional analysis of the correlation between ABCB11 gene mutation and
RT primary intrahepatic stone.";
RL Mol. Med. Report. 19:195-204(2019).
CC -!- FUNCTION: Catalyzes the transport of the major hydrophobic bile salts,
CC such as taurine and glycine-conjugated cholic acid across the
CC canalicular membrane of hepatocytes in an ATP-dependent manner,
CC therefore participates in hepatic bile acid homeostasis and
CC consequently to lipid homeostasis through regulation of biliary lipid
CC secretion in a bile salts dependent manner (PubMed:16332456,
CC PubMed:22262466, PubMed:15791618, PubMed:18985798, PubMed:19228692,
CC PubMed:20398791, PubMed:24711118, PubMed:29507376, PubMed:20010382,
CC PubMed:32203132). Transports taurine-conjugated bile salts more rapidly
CC than glycine-conjugated bile salts (PubMed:16332456). Also transports
CC non-bile acid compounds, such as pravastatin and fexofenadine in an
CC ATP-dependent manner and may be involved in their biliary excretion
CC (PubMed:15901796, PubMed:18245269). {ECO:0000269|PubMed:15791618,
CC ECO:0000269|PubMed:15901796, ECO:0000269|PubMed:16332456,
CC ECO:0000269|PubMed:18245269, ECO:0000269|PubMed:18985798,
CC ECO:0000269|PubMed:19228692, ECO:0000269|PubMed:20010382,
CC ECO:0000269|PubMed:20398791, ECO:0000269|PubMed:22262466,
CC ECO:0000269|PubMed:24711118, ECO:0000269|PubMed:29507376,
CC ECO:0000269|PubMed:32203132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cholate(in) + H2O = ADP + cholate(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:50048, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50049;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurocholate(in) = ADP + H(+) + phosphate +
CC taurocholate(out); Xref=Rhea:RHEA:50052, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36257,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:15901796,
CC ECO:0000269|PubMed:16332456, ECO:0000269|PubMed:18985798,
CC ECO:0000269|PubMed:19228692, ECO:0000269|PubMed:20010382,
CC ECO:0000269|PubMed:20398791, ECO:0000269|PubMed:22262466,
CC ECO:0000269|PubMed:24711118, ECO:0000269|PubMed:29507376,
CC ECO:0000269|PubMed:32203132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50053;
CC Evidence={ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:15901796,
CC ECO:0000269|PubMed:16332456, ECO:0000269|PubMed:18985798,
CC ECO:0000269|PubMed:19228692, ECO:0000269|PubMed:20010382,
CC ECO:0000269|PubMed:20398791, ECO:0000269|PubMed:22262466,
CC ECO:0000269|PubMed:24711118, ECO:0000269|PubMed:29507376,
CC ECO:0000305|PubMed:32203132};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycocholate(in) + H2O = ADP + glycocholate(out) + H(+)
CC + phosphate; Xref=Rhea:RHEA:50056, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29746, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:16332456,
CC ECO:0000269|PubMed:32203132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50057;
CC Evidence={ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:16332456,
CC ECO:0000305|PubMed:32203132};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycochenodeoxycholate(in) + H2O = ADP +
CC glycochenodeoxycholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:50060,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36252, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50061;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurochenodeoxycholate(in) = ADP + H(+) +
CC phosphate + taurochenodeoxycholate(out); Xref=Rhea:RHEA:50064,
CC ChEBI:CHEBI:9407, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50065;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycoursodeoxycholate(in) + H2O = ADP +
CC glycoursodeoxycholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:50068,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:132030, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50069;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + tauroursodeoxycholate(in) = ADP + H(+) + phosphate
CC + tauroursodeoxycholate(out); Xref=Rhea:RHEA:50072,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:132028, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456, ECO:0000269|PubMed:32203132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50073;
CC Evidence={ECO:0000269|PubMed:16332456, ECO:0000305|PubMed:32203132};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurodeoxycholate(in) = ADP + H(+) + phosphate +
CC taurodeoxycholate(out); Xref=Rhea:RHEA:50080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36261,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50081;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurolithocholate 3-sulfate(in) = ADP + H(+) +
CC phosphate + taurolithocholate 3-sulfate(out); Xref=Rhea:RHEA:50084,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58301, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16332456};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50085;
CC Evidence={ECO:0000269|PubMed:16332456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + pravastatin(in) = ADP + H(+) + phosphate +
CC pravastatin(out); Xref=Rhea:RHEA:63908, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:63660, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15901796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63909;
CC Evidence={ECO:0000305|PubMed:15901796};
CC -!- ACTIVITY REGULATION: The uptake of taurocholate is inhibited by
CC taurolithocholate sulfate with an IC(50) of 9 uM (PubMed:16332456).
CC Pravastatin competitively inhibits the transport of taurocholic acid
CC (PubMed:18985798, PubMed:15901796). Cyclosporin A, glibenclamide,
CC rifampicin and troglitazonestrongly competitively inhibit the transport
CC activity of taurocholate (PubMed:18985798, PubMed:32203132). The
CC canalicular transport activity of taurocholate is strongly dependent on
CC canalicular membrane cholesterol content (PubMed:19228692). The uptake
CC of taurocholate is increased by short- and medium-chain fatty acids
CC (PubMed:20398791). Cholesterol increases transport capacity of
CC taurocholate without affecting the affinity for the substrate
CC (PubMed:24711118). {ECO:0000269|PubMed:15901796,
CC ECO:0000269|PubMed:16332456, ECO:0000269|PubMed:18985798,
CC ECO:0000269|PubMed:19228692, ECO:0000269|PubMed:20398791,
CC ECO:0000269|PubMed:24711118, ECO:0000269|PubMed:32203132}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30.4 uM for taurocholate {ECO:0000269|PubMed:17264802};
CC KM=6.2 uM for taurocholate {ECO:0000269|PubMed:16332456};
CC KM=21.7 uM for glycocholate {ECO:0000269|PubMed:16332456};
CC KM=6.6 uM for taurochenodeoxycholate {ECO:0000269|PubMed:16332456};
CC KM=7.5 uM for glycochenodeoxycholate {ECO:0000269|PubMed:16332456};
CC KM=9.5 uM for taurolithocholate sulfate
CC {ECO:0000269|PubMed:16332456};
CC KM=4.61 uM for taurocholate {ECO:0000269|PubMed:15791618};
CC KM=4.64 uM for taurocholate {ECO:0000269|PubMed:15901796};
CC KM=124 uM for pravastatin {ECO:0000269|PubMed:15901796};
CC KM=19.9 uM for taurocholate {ECO:0000269|PubMed:18985798};
CC Vmax=232 pmol/min/mg enzyme for taurocholate transport
CC {ECO:0000269|PubMed:17264802};
CC Vmax=2510 pmol/min/mg enzyme for taurocholate transport
CC {ECO:0000269|PubMed:16332456};
CC Vmax=2310 pmol/min/mg enzyme for taurocholate transport
CC {ECO:0000269|PubMed:15791618};
CC Vmax=4290 pmol/min/mg enzyme for taurocholate transport
CC {ECO:0000269|PubMed:15901796};
CC Vmax=1220 pmol/min/mg enzyme for pravastatin transport
CC {ECO:0000269|PubMed:15901796};
CC Vmax=98.5 pmol/min/mg enzyme for taurocholate transport
CC {ECO:0000269|PubMed:18985798};
CC -!- SUBUNIT: Interacts with HAX1 (By similarity). Interacts with the
CC adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this
CC interaction regulates cell membrane expression of ABCB11 through its
CC internalization in a clathrin-dependent manner and its subsequent
CC degradation (PubMed:22262466). {ECO:0000250|UniProtKB:O70127,
CC ECO:0000269|PubMed:22262466}.
CC -!- INTERACTION:
CC O95342; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-3914067, EBI-742054;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:22262466}; Multi-pass
CC membrane protein {ECO:0000255}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:O70127}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O70127}. Endosome
CC {ECO:0000250|UniProtKB:O70127}. Cell membrane
CC {ECO:0000269|PubMed:20010382, ECO:0000269|PubMed:22262466,
CC ECO:0000269|PubMed:29507376, ECO:0000269|PubMed:30431138}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Internalized at the canalicular
CC membrane through interaction with the adapter protein complex 2 (AP-2)
CC (PubMed:22262466). At steady state, localizes in the canalicular
CC membrane but is also present in recycling endosomes. ABCB11 constantly
CC and rapidly exchanges between the two sites through tubulo-vesicles
CC carriers that move along microtubules. Microtubule-dependent
CC trafficking of ABCB11 is enhanced by taurocholate and cAMP and
CC regulated by STK11 through a PKA-mediated pathway. Trafficking of newly
CC synthesized ABCB11 through endosomal compartment to the bile
CC canalicular membrane is accelerated by cAMP but not by taurocholate (By
CC similarity). Cell membrane expression is up-regulated by short- and
CC medium-chain fatty acids (PubMed:20398791).
CC {ECO:0000250|UniProtKB:O70127, ECO:0000269|PubMed:20398791,
CC ECO:0000269|PubMed:22262466}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly, if not exclusively in the
CC liver, where it was further localized to the canalicular microvilli and
CC to subcanalicular vesicles of the hepatocytes by in situ.
CC -!- DOMAIN: Multifunctional polypeptide with two homologous halves, each
CC containing a hydrophobic membrane-anchoring domain and an ATP binding
CC cassette (ABC) domain.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15791618,
CC ECO:0000269|PubMed:18829893}.
CC -!- PTM: Ubiquitinated; short-chain ubiquitination regulates cell-Surface
CC expression of ABCB11. {ECO:0000269|PubMed:18829893}.
CC -!- DISEASE: Cholestasis, progressive familial intrahepatic, 2 (PFIC2)
CC [MIM:601847]: A disorder characterized by early onset of cholestasis
CC that progresses to hepatic fibrosis, cirrhosis, and end-stage liver
CC disease before adulthood. PFIC2 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:10579978, ECO:0000269|PubMed:11815775,
CC ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:18829893,
CC ECO:0000269|PubMed:20010382, ECO:0000269|PubMed:24969679,
CC ECO:0000269|PubMed:29507376, ECO:0000269|PubMed:9806540}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cholestasis, benign recurrent intrahepatic, 2 (BRIC2)
CC [MIM:605479]: A disorder characterized by intermittent episodes of
CC cholestasis without progression to liver failure. There is initial
CC elevation of serum bile acids, followed by cholestatic jaundice which
CC generally spontaneously resolves after periods of weeks to months. The
CC cholestatic attacks vary in severity and duration. Patients are
CC asymptomatic between episodes, both clinically and biochemically.
CC {ECO:0000269|PubMed:15300568, ECO:0000269|PubMed:16039748,
CC ECO:0000269|PubMed:24711118}. Note=The disease is caused by variants
CC 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 -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
CC ---------------------------------------------------------------------------
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DR EMBL; AF091582; AAC77455.1; -; mRNA.
DR EMBL; AF136523; AAD28285.1; -; mRNA.
DR EMBL; AC008177; AAY24305.1; -; Genomic_DNA.
DR EMBL; AC093723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC069137; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS46444.1; -.
DR RefSeq; NP_003733.2; NM_003742.2.
DR PDB; 6LR0; EM; 3.50 A; U=1-1321.
DR PDB; 7DV5; EM; 3.70 A; U=46-1315.
DR PDB; 7E1A; EM; 3.66 A; U=1-1321.
DR PDBsum; 6LR0; -.
DR PDBsum; 7DV5; -.
DR PDBsum; 7E1A; -.
DR AlphaFoldDB; O95342; -.
DR SMR; O95342; -.
DR BioGRID; 114199; 9.
DR IntAct; O95342; 5.
DR STRING; 9606.ENSP00000263817; -.
DR BindingDB; O95342; -.
DR ChEMBL; CHEMBL6020; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00637; Astemizole.
DR DrugBank; DB01072; Atazanavir.
DR DrugBank; DB00335; Atenolol.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00572; Atropine.
DR DrugBank; DB15233; Avapritinib.
DR DrugBank; DB15719; Belantamab mafodotin.
DR DrugBank; DB12319; Benzbromarone.
DR DrugBank; DB00559; Bosentan.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB01222; Budesonide.
DR DrugBank; DB00833; Cefaclor.
DR DrugBank; DB00482; Celecoxib.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB00477; Chlorpromazine.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB01211; Clarithromycin.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB03619; Deoxycholic acid.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00255; Diethylstilbestrol.
DR DrugBank; DB00390; Digoxin.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB00975; Dipyridamole.
DR DrugBank; DB00822; Disulfiram.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB00199; Erythromycin.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB00301; Flucloxacillin.
DR DrugBank; DB00693; Fluorescein.
DR DrugBank; DB00176; Fluvoxamine.
DR DrugBank; DB02703; Fusidic acid.
DR DrugBank; DB00222; Glimepiride.
DR DrugBank; DB01067; Glipizide.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB02123; Glycochenodeoxycholic Acid.
DR DrugBank; DB13751; Glycyrrhizic acid.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB09374; Indocyanine green acid form.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00270; Isradipine.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB01601; Lopinavir.
DR DrugBank; DB00455; Loratadine.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB00834; Mifepristone.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00698; Nitrofurantoin.
DR DrugBank; DB05990; Obeticholic acid.
DR DrugBank; DB01165; Ofloxacin.
DR DrugBank; DB00275; Olmesartan.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB12712; Pilsicainide.
DR DrugBank; DB08860; Pitavastatin.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB05804; Prasterone sulfate.
DR DrugBank; DB00175; Pravastatin.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB14761; Remdesivir.
DR DrugBank; DB00912; Repaglinide.
DR DrugBank; DB00206; Reserpine.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB00412; Rosiglitazone.
DR DrugBank; DB01098; Rosuvastatin.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB06290; Simeprevir.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB01015; Sulfamethoxazole.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugBank; DB00966; Telmisartan.
DR DrugBank; DB00342; Terfenadine.
DR DrugBank; DB00911; Tinidazole.
DR DrugBank; DB00932; Tipranavir.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB01586; Ursodeoxycholic acid.
DR DrugBank; DB14057; Valinomycin.
DR DrugBank; DB00570; Vinblastine.
DR DrugBank; DB00541; Vincristine.
DR DrugCentral; O95342; -.
DR GuidetoPHARMACOLOGY; 778; -.
DR SwissLipids; SLP:000001597; -.
DR TCDB; 3.A.1.201.2; the atp-binding cassette (abc) superfamily.
DR GlyGen; O95342; 4 sites.
DR iPTMnet; O95342; -.
DR PhosphoSitePlus; O95342; -.
DR BioMuta; ABCB11; -.
DR EPD; O95342; -.
DR jPOST; O95342; -.
DR MassIVE; O95342; -.
DR MaxQB; O95342; -.
DR PaxDb; O95342; -.
DR PeptideAtlas; O95342; -.
DR PRIDE; O95342; -.
DR ProteomicsDB; 50810; -.
DR Antibodypedia; 1033; 241 antibodies from 34 providers.
DR DNASU; 8647; -.
DR Ensembl; ENST00000650372.1; ENSP00000497931.1; ENSG00000073734.10.
DR GeneID; 8647; -.
DR KEGG; hsa:8647; -.
DR MANE-Select; ENST00000650372.1; ENSP00000497931.1; NM_003742.4; NP_003733.2.
DR UCSC; uc002ueo.2; human.
DR CTD; 8647; -.
DR DisGeNET; 8647; -.
DR GeneCards; ABCB11; -.
DR HGNC; HGNC:42; ABCB11.
DR HPA; ENSG00000073734; Tissue enriched (liver).
DR MalaCards; ABCB11; -.
DR MIM; 601847; phenotype.
DR MIM; 603201; gene.
DR MIM; 605479; phenotype.
DR neXtProt; NX_O95342; -.
DR OpenTargets; ENSG00000073734; -.
DR Orphanet; 99961; Benign recurrent intrahepatic cholestasis type 2.
DR Orphanet; 69665; Intrahepatic cholestasis of pregnancy.
DR Orphanet; 79304; Progressive familial intrahepatic cholestasis type 2.
DR PharmGKB; PA374; -.
DR VEuPathDB; HostDB:ENSG00000073734; -.
DR eggNOG; KOG0055; Eukaryota.
DR GeneTree; ENSGT00940000157564; -.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; O95342; -.
DR OMA; LFMLPMT; -.
DR OrthoDB; 186078at2759; -.
DR PhylomeDB; O95342; -.
DR TreeFam; TF105193; -.
DR PathwayCommons; O95342; -.
DR Reactome; R-HSA-159418; Recycling of bile acids and salts.
DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-HSA-5678520; Defective ABCB11 causes PFIC2 and BRIC2.
DR SignaLink; O95342; -.
DR BioGRID-ORCS; 8647; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; ABCB11; human.
DR GeneWiki; ABCB11; -.
DR GenomeRNAi; 8647; -.
DR Pharos; O95342; Tchem.
DR PRO; PR:O95342; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O95342; protein.
DR Bgee; ENSG00000073734; Expressed in right lobe of liver and 96 other tissues.
DR ExpressionAtlas; O95342; baseline and differential.
DR Genevisible; O95342; HS.
DR GO; GO:0016324; C:apical plasma membrane; IMP:UniProtKB.
DR GO; GO:0009986; C:cell surface; IMP:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0046581; C:intercellular canaliculus; IEA:Ensembl.
DR GO; GO:0046691; C:intracellular canaliculus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0015432; F:ABC-type bile acid transporter activity; IDA:UniProtKB.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015126; F:canalicular bile acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015144; F:carbohydrate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0015721; P:bile acid and bile salt transport; IDA:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; TAS:Reactome.
DR GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB.
DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl.
DR GO; GO:0015722; P:canalicular bile acid transport; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0055091; P:phospholipid homeostasis; ISS:UniProtKB.
DR GO; GO:0120189; P:positive regulation of bile acid secretion; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:1904251; P:regulation of bile acid metabolic process; ISS:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:1904486; P:response to 17alpha-ethynylestradiol; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0046618; P:xenobiotic export from cell; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:UniProtKB.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; IMP:UniProtKB.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030278; BSEP.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR PANTHER; PTHR24221:SF165; PTHR24221:SF165; 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; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Disease variant; Endosome;
KW Glycoprotein; Intrahepatic cholestasis; Lipid transport; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..1321
FT /note="Bile salt export pump"
FT /id="PRO_0000093296"
FT TOPO_DOM 1..62
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 84..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 169..215
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 237..240
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 262..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 341..353
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 375..755
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 756..776
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 777..794
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 795..815
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 816..869
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 870..890
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 891..911
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 912..979
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 980..1000
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1001..1011
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1012..1032
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1033..1321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 62..385
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 420..656
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 755..1043
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1078..1316
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 16..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..672
FT /note="Interaction with HAX1"
FT /evidence="ECO:0000250"
FT REGION 1311..1314
FT /note="Mediates internalization from the plasma membrane"
FT /evidence="ECO:0000269|PubMed:22262466"
FT BINDING 455..462
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1113..1120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 586
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 690
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QY30"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70127"
FT MOD_RES 704
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1214
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70127"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17082223"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17082223"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17082223"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17082223"
FT VARIANT 56
FT /note="S -> L (does not affect taurocholate transport
FT activity; does not affect cell surface protein expression;
FT dbSNP:rs11568361)"
FT /evidence="ECO:0000269|PubMed:20010382"
FT /id="VAR_055472"
FT VARIANT 129
FT /note="C -> Y (in PFIC2; loss of cell membrane
FT localization; significantly reduces taurocholate transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:29507376"
FT /id="VAR_083783"
FT VARIANT 186
FT /note="E -> G (in BRIC2; dbSNP:rs72551307)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030386"
FT VARIANT 206
FT /note="I -> V (impairs taurocholate transport activity;
FT does not affect protein expression; does not affect cell
FT surface protein expression; does not affect cell membrane
FT localization; dbSNP:rs11568357)"
FT /evidence="ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:20010382"
FT /id="VAR_030387"
FT VARIANT 238
FT /note="G -> V (in PFIC2; dbSNP:rs72551306)"
FT /evidence="ECO:0000269|PubMed:10579978"
FT /id="VAR_030388"
FT VARIANT 284
FT /note="V -> A (in dbSNP:rs200739891)"
FT /evidence="ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:17264802"
FT /id="VAR_035349"
FT VARIANT 284
FT /note="V -> L (in PFIC2)"
FT /evidence="ECO:0000269|PubMed:11815775"
FT /id="VAR_013332"
FT VARIANT 297
FT /note="E -> G (in PFIC2 and BRIC2; reduces transport
FT capacity for taurocholate; decreases protein expression;
FT affects maturation of protein in the reticulum endoplasmic;
FT does not affect apical membrane localization; does not
FT affect cell surface expression of the mature form; does not
FT affect transport of taurocholate and glycocholate; enhances
FT ubiquitination susceptibility; reduces transport activity
FT of taurocholate in a low cholesterol environment; increases
FT transport activity of taurocholate in a high cholesterol
FT environment; does not affect protein expression; does not
FT affect cell membrane localization; dbSNP:rs11568372)"
FT /evidence="ECO:0000269|PubMed:15300568,
FT ECO:0000269|PubMed:15791618, ECO:0000269|PubMed:16039748,
FT ECO:0000269|PubMed:18829893, ECO:0000269|PubMed:20010382,
FT ECO:0000269|PubMed:24711118, ECO:0000269|PubMed:9806540"
FT /id="VAR_010271"
FT VARIANT 299
FT /note="R -> K (in dbSNP:rs2287617)"
FT /evidence="ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:30431138"
FT /id="VAR_030389"
FT VARIANT 336
FT /note="C -> S (in PFIC2; dbSNP:rs72551305)"
FT /evidence="ECO:0000269|PubMed:10579978"
FT /id="VAR_030390"
FT VARIANT 337
FT /note="Y -> H (in PFIC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073967"
FT VARIANT 415
FT /note="R -> Q (in dbSNP:rs371656014)"
FT /evidence="ECO:0000269|PubMed:15077010"
FT /id="VAR_043074"
FT VARIANT 432
FT /note="R -> T (in BRIC2; reduced transport capacity for
FT taurocholate; reduces transport activity of taurocholate in
FT a low cholesterol environment; increases transport activity
FT of taurocholate in a high cholesterol environment;
FT dbSNP:rs121908935)"
FT /evidence="ECO:0000269|PubMed:16039748,
FT ECO:0000269|PubMed:24711118"
FT /id="VAR_030391"
FT VARIANT 444
FT /note="V -> A (more frequent in patients with drug-induced
FT cholestasis than healthy controls; associated with lower
FT hepatic expression; does not affect transport capacity for
FT taurocholate; increases transport activity of taurocholate
FT in a low cholesterol environment; increases transport
FT activity of taurocholate in a high cholesterol environment;
FT does not affect cell surface protein expression; does not
FT affect protein expression; dbSNP:rs2287622)"
FT /evidence="ECO:0000269|PubMed:11829140,
FT ECO:0000269|PubMed:15077010, ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:16799996, ECO:0000269|PubMed:17264802,
FT ECO:0000269|PubMed:20010382, ECO:0000269|PubMed:24711118,
FT ECO:0000269|PubMed:24969679, ECO:0000269|PubMed:30431138,
FT ECO:0000269|Ref.2"
FT /id="VAR_013333"
FT VARIANT 444
FT /note="V -> D (in dbSNP:rs2287622)"
FT /id="VAR_059106"
FT VARIANT 444
FT /note="V -> G (in dbSNP:rs2287622)"
FT /id="VAR_059107"
FT VARIANT 461
FT /note="K -> E (in PFIC2; dbSNP:rs1274558905)"
FT /evidence="ECO:0000269|PubMed:9806540"
FT /id="VAR_013334"
FT VARIANT 472
FT /note="Y -> C (in PFIC2; dbSNP:rs369860506)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073968"
FT VARIANT 482
FT /note="D -> G (in PFIC2; decreases protein expression;
FT affects maturation of protein in the reticulum endoplasmic;
FT decreases apical membrane localization; affects cell
FT surface expression; does not affect transport of
FT taurocholate and glycocholate; enhances ubiquitination
FT susceptibility; dbSNP:rs72549402)"
FT /evidence="ECO:0000269|PubMed:15791618,
FT ECO:0000269|PubMed:18829893, ECO:0000269|PubMed:9806540"
FT /id="VAR_013335"
FT VARIANT 558
FT /note="Q -> H (impairs taurocholate transport activity;
FT does not affect protein expression; does not affect cell
FT surface protein expression; does not affect cell membrane
FT localization; dbSNP:rs11568369)"
FT /evidence="ECO:0000269|PubMed:20010382"
FT /id="VAR_083784"
FT VARIANT 570
FT /note="A -> T (in BRIC2; dbSNP:rs886043807)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030392"
FT VARIANT 591
FT /note="N -> S (in a patient with intrahepatic cholestasis
FT of pregnancy; impairs taurocholate transport activity; does
FT not affect protein expression; does not affect cell surface
FT protein expression; does not affect cell membrane
FT localization; dbSNP:rs11568367)"
FT /evidence="ECO:0000269|PubMed:15077010,
FT ECO:0000269|PubMed:20010382"
FT /id="VAR_043075"
FT VARIANT 592
FT /note="E -> Q (does not affect taurocholate transport
FT activity; does not affect protein expression; does not
FT affect cell surface protein expression; dbSNP:rs11568370)"
FT /evidence="ECO:0000269|PubMed:20010382"
FT /id="VAR_083785"
FT VARIANT 616
FT /note="R -> G"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_035350"
FT VARIANT 619
FT /note="T -> A (in dbSNP:rs912519986)"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_035351"
FT VARIANT 676
FT /note="D -> Y (in fluvastatin-induced cholestasis; does not
FT affect transport capacity for taurocholate)"
FT /evidence="ECO:0000269|PubMed:17264802"
FT /id="VAR_043076"
FT VARIANT 677
FT /note="M -> V (does not affect taurocholate transport
FT activity; does not affect protein expression; does not
FT affect cell surface protein expression; dbSNP:rs11568364)"
FT /evidence="ECO:0000269|PubMed:15077010,
FT ECO:0000269|PubMed:16763017, ECO:0000269|PubMed:16799996,
FT ECO:0000269|PubMed:17264802, ECO:0000269|PubMed:20010382"
FT /id="VAR_030393"
FT VARIANT 696
FT /note="R -> W (in PFIC2; unknown pathological significance;
FT dbSNP:rs376216286)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073969"
FT VARIANT 698
FT /note="R -> H (in dbSNP:rs138642043)"
FT /evidence="ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:17264802"
FT /id="VAR_035352"
FT VARIANT 855
FT /note="G -> R (in ethinylestradiol/gestodene-induced
FT cholestasis; loss of transport capacity for taurocholate)"
FT /evidence="ECO:0000269|PubMed:17264802"
FT /id="VAR_043077"
FT VARIANT 865
FT /note="A -> V (might be associated with increased risk of
FT intrahepatic stones; decreases protein expression;
FT deacreases localization to the cell membrane; decreases the
FT trafficking to the plasma membrane; dbSNP:rs118109635)"
FT /evidence="ECO:0000269|PubMed:16763017,
FT ECO:0000269|PubMed:24969679, ECO:0000269|PubMed:30431138"
FT /id="VAR_035353"
FT VARIANT 923
FT /note="T -> P (in BRIC2; dbSNP:rs777469571)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030394"
FT VARIANT 926
FT /note="A -> P (in BRIC2; dbSNP:rs72549400)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030395"
FT VARIANT 931
FT /note="Q -> P (in PFIC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073970"
FT VARIANT 958
FT /note="R -> Q (in dbSNP:rs761363245)"
FT /evidence="ECO:0000269|PubMed:16763017"
FT /id="VAR_035354"
FT VARIANT 982
FT /note="G -> R (in PFIC2; impairs taurocholate transport
FT activity; significantly reduces protein expression;
FT decreases cell surface protein expression; loss of ell
FT membrane localization; dbSNP:rs72549399)"
FT /evidence="ECO:0000269|PubMed:20010382,
FT ECO:0000269|PubMed:9806540"
FT /id="VAR_013336"
FT VARIANT 1004
FT /note="G -> D (in PFIC2)"
FT /evidence="ECO:0000269|PubMed:11815775"
FT /id="VAR_013337"
FT VARIANT 1050
FT /note="R -> C (in BRIC2; dbSNP:rs72549398)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030396"
FT VARIANT 1128
FT /note="R -> H (in BRIC2; dbSNP:rs756220860)"
FT /evidence="ECO:0000269|PubMed:15300568"
FT /id="VAR_030397"
FT VARIANT 1131
FT /note="D -> V (in PFIC2)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073971"
FT VARIANT 1153
FT /note="R -> C (in PFIC2; impairs taurocholate transport
FT activity; significantly reduces protein expression;
FT decreases cell surface protein expression; loss of ell
FT membrane localization; dbSNP:rs72549395)"
FT /evidence="ECO:0000269|PubMed:20010382,
FT ECO:0000269|PubMed:9806540"
FT /id="VAR_013338"
FT VARIANT 1186
FT /note="E -> K (impairs taurocholate transport activity;
FT does not affect protein expression; decreases cell surface
FT protein expression; reduces plasma membrane localization;
FT dbSNP:rs1521808)"
FT /evidence="ECO:0000269|PubMed:20010382"
FT /id="VAR_030398"
FT VARIANT 1198
FT /note="H -> R (in PFIC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24969679"
FT /id="VAR_073972"
FT VARIANT 1268
FT /note="R -> Q (in PFIC2; dbSNP:rs72549394)"
FT /evidence="ECO:0000269|PubMed:9806540"
FT /id="VAR_013339"
FT MUTAGEN 1..441
FT /note="Missing: Does not affect ATPase-coupled bile acid
FT transport activity. Decreases protein stability."
FT /evidence="ECO:0000269|PubMed:32203132"
FT MUTAGEN 1311
FT /note="Y->A: Loss of interaction with AP2A1 and AP2A2.
FT Promotes ABCB11 plasma membrane trafficking. Does not
FT affect plasma membrane localization. Inhibits ABCB11
FT internalization."
FT /evidence="ECO:0000269|PubMed:22262466"
FT CONFLICT 339
FT /note="L -> V (in Ref. 1; AAC77455)"
FT /evidence="ECO:0000305"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 71..75
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 80..83
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 84..88
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 89..99
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 141..147
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 148..154
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 155..160
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 162..170
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 174..182
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 212..220
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 231..237
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 249..256
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 267..274
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 288..293
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 294..308
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 314..320
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 336..343
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 344..348
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 349..352
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 364..375
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 378..385
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 386..390
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 420..427
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 437..445
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 449..452
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 456..462
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 463..466
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 467..470
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 479..486
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 491..494
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 497..501
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 513..518
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 526..534
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 538..540
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 544..548
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 553..557
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 561..563
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 564..574
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 578..584
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 594..602
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 607..613
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 617..619
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 620..622
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 630..632
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 641..645
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 648..652
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 653..655
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 688..700
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 701..703
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 711..714
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 743..746
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 749..751
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 752..762
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 763..768
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 769..775
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 776..779
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 790..801
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 803..805
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 807..810
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 811..813
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 815..817
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 820..822
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 825..827
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 829..832
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 833..835
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 836..838
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 839..841
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 844..846
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 849..852
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 854..856
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 858..860
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 861..868
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 869..875
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 876..880
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 881..885
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 886..896
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 898..903
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 905..907
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 909..912
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 913..917
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 920..925
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 926..929
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 930..935
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 936..939
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 941..944
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 947..950
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 957..961
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 962..973
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 974..979
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 980..988
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 989..991
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 992..994
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 995..1006
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1007..1010
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1014..1016
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1017..1020
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1021..1023
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1026..1028
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1029..1031
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1032..1034
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1038..1042
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1043..1048
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1049..1052
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1079..1082
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1092..1094
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1115..1120
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1121..1124
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1127..1130
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1137..1142
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1144..1147
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1149..1152
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1155..1159
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1172..1175
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1179..1181
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1186..1190
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1193..1196
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1198..1200
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1201..1203
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1204..1208
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1213..1216
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1221..1223
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1225..1232
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1238..1242
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1251..1263
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1266..1269
FT /evidence="ECO:0007829|PDB:6LR0"
FT STRAND 1299..1302
FT /evidence="ECO:0007829|PDB:6LR0"
FT TURN 1303..1305
FT /evidence="ECO:0007829|PDB:6LR0"
FT HELIX 1309..1313
FT /evidence="ECO:0007829|PDB:6LR0"
SQ SEQUENCE 1321 AA; 146407 MW; 61EE2173E2351D80 CRC64;
MSDSVILRSI KKFGEENDGF ESDKSYNNDK KSRLQDEKKG DGVRVGFFQL FRFSSSTDIW
LMFVGSLCAF LHGIAQPGVL LIFGTMTDVF IDYDVELQEL QIPGKACVNN TIVWTNSSLN
QNMTNGTRCG LLNIESEMIK FASYYAGIAV AVLITGYIQI CFWVIAAARQ IQKMRKFYFR
RIMRMEIGWF DCNSVGELNT RFSDDINKIN DAIADQMALF IQRMTSTICG FLLGFFRGWK
LTLVIISVSP LIGIGAATIG LSVSKFTDYE LKAYAKAGVV ADEVISSMRT VAAFGGEKRE
VERYEKNLVF AQRWGIRKGI VMGFFTGFVW CLIFLCYALA FWYGSTLVLD EGEYTPGTLV
QIFLSVIVGA LNLGNASPCL EAFATGRAAA TSIFETIDRK PIIDCMSEDG YKLDRIKGEI
EFHNVTFHYP SRPEVKILND LNMVIKPGEM TALVGPSGAG KSTALQLIQR FYDPCEGMVT
VDGHDIRSLN IQWLRDQIGI VEQEPVLFST TIAENIRYGR EDATMEDIVQ AAKEANAYNF
IMDLPQQFDT LVGEGGGQMS GGQKQRVAIA RALIRNPKIL LLDMATSALD NESEAMVQEV
LSKIQHGHTI ISVAHRLSTV RAADTIIGFE HGTAVERGTH EELLERKGVY FTLVTLQSQG
NQALNEEDIK DATEDDMLAR TFSRGSYQDS LRASIRQRSK SQLSYLVHEP PLAVVDHKST
YEEDRKDKDI PVQEEVEPAP VRRILKFSAP EWPYMLVGSV GAAVNGTVTP LYAFLFSQIL
GTFSIPDKEE QRSQINGVCL LFVAMGCVSL FTQFLQGYAF AKSGELLTKR LRKFGFRAML
GQDIAWFDDL RNSPGALTTR LATDASQVQG AAGSQIGMIV NSFTNVTVAM IIAFSFSWKL
SLVILCFFPF LALSGATQTR MLTGFASRDK QALEMVGQIT NEALSNIRTV AGIGKERRFI
EALETELEKP FKTAIQKANI YGFCFAFAQC IMFIANSASY RYGGYLISNE GLHFSYVFRV
ISAVVLSATA LGRAFSYTPS YAKAKISAAR FFQLLDRQPP ISVYNTAGEK WDNFQGKIDF
VDCKFTYPSR PDSQVLNGLS VSISPGQTLA FVGSSGCGKS TSIQLLERFY DPDQGKVMID
GHDSKKVNVQ FLRSNIGIVS QEPVLFACSI MDNIKYGDNT KEIPMERVIA AAKQAQLHDF
VMSLPEKYET NVGSQGSQLS RGEKQRIAIA RAIVRDPKIL LLDEATSALD TESEKTVQVA
LDKAREGRTC IVIAHRLSTI QNADIIAVMA QGVVIEKGTH EELMAQKGAY YKLVTTGSPI
S
