Reviewed, UniProtKB/Swiss-Prot O95342 (ABCBB_HUMAN)

Names and origin

Protein names

Recommended name:
    Bile salt export pump
Alternative name(s):
    ATP-binding cassette sub-family B member 11

Gene names

Name:	ABCB11
Synonyms:	BSEP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1321 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ By similarity.
Domain	Multifunctional polypeptide with two homologous halves, each containing an hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
Involvement in disease	Defects in ABCB11 are the cause of progressive familial intrahepatic cholestasis type 2 (PFIC2) [MIM:601847]. PFIC2 is an inherited liver disease of childhood which is characterized by cholestasis and normal serum gamma-glutamyltransferase activity. Defects in ABCB11 are also found in cases of chronic intrahepatic cholestasis without obvious familial history of chronic liver disease. Ref.1 Ref.3 Ref.5 Defects in ABCB11 are the cause of benign recurrent intrahepatic cholestasis type 2 (BRIC2) [MIM:605479]. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration and patients are asymptomatic between episodes, both clinically and biochemically. Ref.6 Ref.8 Genetic variations in ABCB11 may play a role in drug-induced cholestasis causing liver damage.
Sequence similarities	Belongs to the ABC transporter family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.
biophysicochemical properties	Kinetic parameters: KM=30.4 µM for taurocholate Vmax=232 pmol/min/mg enzyme for taurocholate transport

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Intrahepatic cholestasis
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	transport Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc membrane fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Ref.1 Traceable author statement. Source: ProtInc bile acid-exporting ATPase activity Ref.1 Traceable author statement. Source: ProtInc sodium-exporting ATPase activity, phosphorylative mechanism Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1321	1321	Bile salt export pump		PRO_0000093296
Regions
	Topological domain	1 – 62	62	Cytoplasmic Potential
	Transmembrane	63 – 83	21	Potential
	Topological domain	84 – 147	64	Extracellular Potential
	Transmembrane	148 – 168	21	Potential
	Topological domain	169 – 215	47	Cytoplasmic Potential
	Transmembrane	216 – 236	21	Potential
	Topological domain	237 – 240	4	Extracellular Potential
	Transmembrane	241 – 261	21	Potential
	Topological domain	262 – 319	58	Cytoplasmic Potential
	Transmembrane	320 – 340	21	Potential
	Topological domain	341 – 353	13	Extracellular Potential
	Transmembrane	354 – 374	21	Potential
	Topological domain	375 – 755	381	Cytoplasmic Potential
	Transmembrane	756 – 776	21	Potential
	Topological domain	777 – 794	18	Extracellular Potential
	Transmembrane	795 – 815	21	Potential
	Topological domain	816 – 869	54	Cytoplasmic Potential
	Transmembrane	870 – 890	21	Potential
	Transmembrane	891 – 911	21	Potential
	Topological domain	912 – 979	68	Cytoplasmic Potential
	Transmembrane	980 – 1000	21	Potential
	Topological domain	1001 – 1011	11	Extracellular Potential
	Transmembrane	1012 – 1032	21	Potential
	Topological domain	1033 – 1321	289	Cytoplasmic Potential
	Domain	62 – 385	324	ABC transmembrane type-1 1
	Domain	420 – 656	237	ABC transporter 1
	Domain	755 – 1043	289	ABC transmembrane type-1 2
	Domain	1078 – 1316	239	ABC transporter 2
	Nucleotide binding	455 – 462	8	ATP 1 Potential
	Nucleotide binding	1113 – 1120	8	ATP 2 Potential
Amino acid modifications
	Modified residue	690	1	Phosphoserine By similarity
	Modified residue	694	1	Phosphoserine By similarity
	Modified residue	701	1	Phosphoserine By similarity
	Glycosylation	109	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	56	1	S → L: dbSNP rs11568361.		VAR_055472
	Natural variant	186	1	E → G in BRIC2. Ref.6		VAR_030386
	Natural variant	206	1	I → V: dbSNP rs11568357. Ref.9		VAR_030387
	Natural variant	238	1	G → V in PFIC2. Ref.3		VAR_030388
	Natural variant	284	1	V → A Ref.5 Ref.9 Ref.11		VAR_035349
	Natural variant	284	1	V → L in PFIC2. Ref.5		VAR_013332
	Natural variant	297	1	E → G in PFIC2 and BRIC2; reduced transport capacity for taurocholate.		VAR_010271
	Natural variant	299	1	R → K: dbSNP rs2287617. Ref.9		VAR_030389
	Natural variant	336	1	C → S in PFIC2. Ref.3		VAR_030390
	Natural variant	415	1	R → Q Ref.7		VAR_043074
	Natural variant	432	1	R → T in BRIC2; reduced transport capacity for taurocholate. Ref.8		VAR_030391
	Natural variant	444	1	V → A More frequent in patients with drug-induced cholestasis than healthy controls; associated with lower hepatic expression; does not affect transport capacity for taurocholate. dbSNP rs2287622. Ref.9 Ref.11 Ref.7 Ref.4 Ref.10		VAR_013333
	Natural variant	461	1	K → E in PFIC2. Ref.1		VAR_013334
	Natural variant	482	1	D → G in PFIC2. Ref.1		VAR_013335
	Natural variant	570	1	A → T in BRIC2. Ref.6		VAR_030392
	Natural variant	591	1	N → S in a patient with intrahepatic cholestasis of pregnancy. Ref.7		VAR_043075
	Natural variant	616	1	R → G Ref.9		VAR_035350
	Natural variant	619	1	T → A Ref.9		VAR_035351
	Natural variant	676	1	D → Y in fluvastatin-induced cholestasis; does not affect transport capacity for taurocholate. Ref.11		VAR_043076
	Natural variant	677	1	M → V Does not affect transport capacity for taurocholate. dbSNP rs11568364. Ref.9 Ref.11 Ref.7 Ref.10		VAR_030393
	Natural variant	698	1	R → H Ref.9 Ref.11		VAR_035352
	Natural variant	855	1	G → R in ethinylestradiol/gestodene-induced cholestasis; loss of transport capacity for taurocholate. Ref.11		VAR_043077
	Natural variant	865	1	A → V Ref.9		VAR_035353
	Natural variant	923	1	T → P in BRIC2. Ref.6		VAR_030394
	Natural variant	926	1	A → P in BRIC2. Ref.6		VAR_030395
	Natural variant	958	1	R → Q Ref.9		VAR_035354
	Natural variant	982	1	G → R in PFIC2. Ref.1		VAR_013336
	Natural variant	1004	1	G → D in PFIC2. Ref.5		VAR_013337
	Natural variant	1050	1	R → C in BRIC2. Ref.6		VAR_030396
	Natural variant	1128	1	R → H in BRIC2. Ref.6		VAR_030397
	Natural variant	1153	1	R → C in PFIC2. Ref.1		VAR_013338
	Natural variant	1186	1	E → K: dbSNP rs1521808.		VAR_030398
	Natural variant	1268	1	R → Q in PFIC2. Ref.1		VAR_013339
Experimental info
	Sequence conflict	339	1	V → L in AAD28285. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O95342-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: D444CACC48DEA371	FASTA	1,321	146,393
	10 20 30 40 50 60 MSDSVILRSI KKFGEENDGF ESDKSYNNDK KSRLQDEKKG DGVRVGFFQL FRFSSSTDIW 70 80 90 100 110 120 LMFVGSLCAF LHGIAQPGVL LIFGTMTDVF IDYDVELQEL QIPGKACVNN TIVWTNSSLN 130 140 150 160 170 180 QNMTNGTRCG LLNIESEMIK FASYYAGIAV AVLITGYIQI CFWVIAAARQ IQKMRKFYFR 190 200 210 220 230 240 RIMRMEIGWF DCNSVGELNT RFSDDINKIN DAIADQMALF IQRMTSTICG FLLGFFRGWK 250 260 270 280 290 300 LTLVIISVSP LIGIGAATIG LSVSKFTDYE LKAYAKAGVV ADEVISSMRT VAAFGGEKRE 310 320 330 340 350 360 VERYEKNLVF AQRWGIRKGI VMGFFTGFVW CLIFLCYAVA FWYGSTLVLD EGEYTPGTLV 370 380 390 400 410 420 QIFLSVIVGA LNLGNASPCL EAFATGRAAA TSIFETIDRK PIIDCMSEDG YKLDRIKGEI 430 440 450 460 470 480 EFHNVTFHYP SRPEVKILND LNMVIKPGEM TALVGPSGAG KSTALQLIQR FYDPCEGMVT 490 500 510 520 530 540 VDGHDIRSLN IQWLRDQIGI VEQEPVLFST TIAENIRYGR EDATMEDIVQ AAKEANAYNF 550 560 570 580 590 600 IMDLPQQFDT LVGEGGGQMS GGQKQRVAIA RALIRNPKIL LLDMATSALD NESEAMVQEV 610 620 630 640 650 660 LSKIQHGHTI ISVAHRLSTV RAADTIIGFE HGTAVERGTH EELLERKGVY FTLVTLQSQG 670 680 690 700 710 720 NQALNEEDIK DATEDDMLAR TFSRGSYQDS LRASIRQRSK SQLSYLVHEP PLAVVDHKST 730 740 750 760 770 780 YEEDRKDKDI PVQEEVEPAP VRRILKFSAP EWPYMLVGSV GAAVNGTVTP LYAFLFSQIL 790 800 810 820 830 840 GTFSIPDKEE QRSQINGVCL LFVAMGCVSL FTQFLQGYAF AKSGELLTKR LRKFGFRAML 850 860 870 880 890 900 GQDIAWFDDL RNSPGALTTR LATDASQVQG AAGSQIGMIV NSFTNVTVAM IIAFSFSWKL 910 920 930 940 950 960 SLVILCFFPF LALSGATQTR MLTGFASRDK QALEMVGQIT NEALSNIRTV AGIGKERRFI 970 980 990 1000 1010 1020 EALETELEKP FKTAIQKANI YGFCFAFAQC IMFIANSASY RYGGYLISNE GLHFSYVFRV 1030 1040 1050 1060 1070 1080 ISAVVLSATA LGRAFSYTPS YAKAKISAAR FFQLLDRQPP ISVYNTAGEK WDNFQGKIDF 1090 1100 1110 1120 1130 1140 VDCKFTYPSR PDSQVLNGLS VSISPGQTLA FVGSSGCGKS TSIQLLERFY DPDQGKVMID 1150 1160 1170 1180 1190 1200 GHDSKKVNVQ FLRSNIGIVS QEPVLFACSI MDNIKYGDNT KEIPMERVIA AAKQAQLHDF 1210 1220 1230 1240 1250 1260 VMSLPEKYET NVGSQGSQLS RGEKQRIAIA RAIVRDPKIL LLDEATSALD TESEKTVQVA 1270 1280 1290 1300 1310 1320 LDKAREGRTC IVIAHRLSTI QNADIIAVMA QGVVIEKGTH EELMAQKGAY YKLVTTGSPI S

References

[1]	"A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis." Strautnieks S.S., Bull L.N., Knisely A.S., Kocoshis S.A., Dahl N., Arnell H., Sokal E.M., Dahan K., Childs S., Ling V., Tanner M.S., Kagalwalla A.F., Nemeth A., Pawlowska J., Baker A., Mieli-Vergani G., Freimer N.B., Gardiner R.M., Thompson R.J. Nat. Genet. 20:233-238(1998) [PubMed: 9806540] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PFIC2 GLY-297; GLU-461; GLY-482; ARG-982; CYS-1153 AND GLN-1268.
[2]	"Cellular localization and functional characterization of the human bile salt export pump (BSEP)." Mol O., Hooiveld G.J.E.J., Jansen P.L.M., Muller M. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis." Jansen P.L.M., Strautnieks S.S., Jacquemin E., Hadchouel M., Sokal E.M., Hooiveld G.J.E.J., Koning J.H., De Jager-Krikken A., Kuipers F., Stellaard F., Bijleveld C.M., Gouw A., Van Goor H., Thompson R.J., Muller M. Gastroenterology 117:1370-1379(1999) [PubMed: 10579978] [Abstract] Cited for: VARIANTS PFIC2 VAL-238 AND SER-336.
[4]	"Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population." Saito S., Iida A., Sekine A., Miura Y., Ogawa C., Kawauchi S., Higuchi S., Nakamura Y. J. Hum. Genet. 47:38-50(2002) [PubMed: 11829140] [Abstract] Cited for: VARIANT ALA-444.
[5]	"FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase levels." Chen H.-L., Chang P.-S., Hsu H.-C., Ni Y.-H., Hsu H.-Y., Lee J.-H., Jeng Y.-M., Shau W.-Y., Chang M.-H. J. Pediatr. 140:119-124(2002) [PubMed: 11815775] [Abstract] Cited for: VARIANTS PFIC2 LEU-284 AND ASP-1004.
[6]	"Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11." van Mil S.W.C., van der Woerd W.L., van der Brugge G., Sturm E., Jansen P.L.M., Bull L.N., van den Berg I.E.T., Berger R., Houwen R.H.J., Klomp L.W.J. Gastroenterology 127:379-384(2004) [PubMed: 15300568] [Abstract] Cited for: VARIANTS BRIC2 GLY-186; GLY-297; THR-570; PRO-923; PRO-926; CYS-1050 AND HIS-1128.
[7]	"Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy." Pauli-Magnus C., Lang T., Meier Y., Zodan-Marin T., Jung D., Breymann C., Zimmermann R., Kenngott S., Beuers U., Reichel C., Kerb R., Penger A., Meier P.J., Kullak-Ublick G.A. Pharmacogenetics 14:91-102(2004) [PubMed: 15077010] [Abstract] Cited for: VARIANTS GLN-415; ALA-444; SER-591 AND VAL-677.
[8]	"Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis." Noe J., Kullak-Ublick G.A., Jochum W., Stieger B., Kerb R., Haberl M., Muellhaupt B., Meier P.J., Pauli-Magnus C. J. Hepatol. 43:536-543(2005) [PubMed: 16039748] [Abstract] Cited for: VARIANTS BRIC2 GLY-297 AND THR-432, CHARACTERIZATION OF VARIANTS BRIC2 GLY-297 AND THR-432.
[9]	"Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11)." Lang T., Haberl M., Jung D., Drescher A., Schlagenhaufer R., Keil A., Mornhinweg E., Stieger B., Kullak-Ublick G.A., Kerb R. Drug Metab. Dispos. 34:1582-1599(2006) [PubMed: 16763017] [Abstract] Cited for: VARIANTS VAL-206; ALA-284; LYS-299; ALA-444; GLY-616; ALA-619; VAL-677; HIS-698; VAL-865 AND GLN-958.
[10]	"Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver." Meier Y., Pauli-Magnus C., Zanger U.M., Klein K., Schaeffeler E., Nussler A.K., Nussler N., Eichelbaum M., Meier P.J., Stieger B. Hepatology 44:62-74(2006) [PubMed: 16799996] [Abstract] Cited for: VARIANTS ALA-444 AND VAL-677.
[11]	"Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury." Lang C., Meier Y., Stieger B., Beuers U., Lang T., Kerb R., Kullak-Ublick G.A., Meier P.J., Pauli-Magnus C. Pharmacogenet. Genomics 17:47-60(2007) [PubMed: 17264802] [Abstract] Cited for: VARIANTS ALA-284; ALA-444; TYR-676; VAL-677; HIS-698 AND ARG-855, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS ALA-444; TYR-676; VAL-677 AND ARG-855, INVOLVEMENT IN DRUG-INDUCED CHOLESTASIS.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF091582 mRNA. Translation: AAC77455.1. AF136523 mRNA. Translation: AAD28285.1.
IPI	IPI00184848.
RefSeq	NP_003733.2.
UniGene	Hs.658439
3D structure databases
HSSP	HSSP built from PDB template 1MT0 based on UniProtKB P08716.
ModBase	Search...
Protein family/group databases
TCDB	3.A.1.201.2. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	O95342.
Proteomic databases
PRIDE	O95342.
Genome annotation databases
Ensembl	ENSG00000073734. Homo sapiens. [Contig view]
GeneID	8647.
KEGG	hsa:8647.
Organism-specific databases
GeneCards	GC02M169487.
HGNC	HGNC:42. ABCB11.
HPA	HPA019035.
MIM	601847. phenotype. 603201. gene. 605479. phenotype.
Orphanet	172. Cholestasis, progressive familial intrahepatic. 79304. Cholestasis, progressive familial intrahepatic 2.
PharmGKB	PA374.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95342.
HOVERGEN	O95342.
Enzyme and pathway databases
Reactome	REACT_602. Lipid and lipoprotein metabolism.
Gene expression databases
ArrayExpress	O95342.
Bgee	O95342.
CleanEx	HS_ABCB11.
GermOnline	ENSG00000073734. Homo sapiens.
Family and domain databases
InterPro	IPR001140. ABC_TM_transpt. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR003593. ATPase_AAA+_core. [Graphical view]
Pfam	PF00664. ABC_membrane. 2 hits. PF00005. ABC_tran. 2 hits. [Graphical view]
ProDom	PD000006. ABC_transporter. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00382. AAA. 2 hits. [Graphical view]
PROSITE	PS50929. ABC_TM1F. 2 hits. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00171. Adenosine triphosphate. DB00559. Bosentan. DB01016. Glibenclamide.
NextBio	32419.
SOURCE	Search...

Entry information

Entry name

ABCBB_HUMAN

Accession

Primary (citable) accession number: O95342
Secondary accession number(s): Q9UNB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 1, 1999
Last modified:	May 26, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)