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Reviewed, UniProtKB/Swiss-Prot O95342 (ABCBB_HUMAN)

Last modified May 26, 2009. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Bile salt export pump
Alternative name(s):
    ATP-binding cassette sub-family B member 11
Gene names
Name: ABCB11
Synonyms: BSEP
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1321 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13211321Bile salt export pump
PRO_0000093296

Regions

Topological domain1 – 6262Cytoplasmic Potential
Transmembrane63 – 8321 Potential
Topological domain84 – 14764Extracellular Potential
Transmembrane148 – 16821 Potential
Topological domain169 – 21547Cytoplasmic Potential
Transmembrane216 – 23621 Potential
Topological domain237 – 2404Extracellular Potential
Transmembrane241 – 26121 Potential
Topological domain262 – 31958Cytoplasmic Potential
Transmembrane320 – 34021 Potential
Topological domain341 – 35313Extracellular Potential
Transmembrane354 – 37421 Potential
Topological domain375 – 755381Cytoplasmic Potential
Transmembrane756 – 77621 Potential
Topological domain777 – 79418Extracellular Potential
Transmembrane795 – 81521 Potential
Topological domain816 – 86954Cytoplasmic Potential
Transmembrane870 – 89021 Potential
Transmembrane891 – 91121 Potential
Topological domain912 – 97968Cytoplasmic Potential
Transmembrane980 – 100021 Potential
Topological domain1001 – 101111Extracellular Potential
Transmembrane1012 – 103221 Potential
Topological domain1033 – 1321289Cytoplasmic Potential
Domain62 – 385324ABC transmembrane type-1 1
Domain420 – 656237ABC transporter 1
Domain755 – 1043289ABC transmembrane type-1 2
Domain1078 – 1316239ABC transporter 2
Nucleotide binding455 – 4628ATP 1 Potential
Nucleotide binding1113 – 11208ATP 2 Potential

Amino acid modifications

Modified residue6901Phosphoserine By similarity
Modified residue6941Phosphoserine By similarity
Modified residue7011Phosphoserine By similarity
Glycosylation1091N-linked (GlcNAc...) Potential
Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential

Natural variations

Natural variant561S → L: dbSNP rs11568361.
VAR_055472
Natural variant1861E → G in BRIC2. Ref.6
VAR_030386
Natural variant2061I → V: dbSNP rs11568357. Ref.9
VAR_030387
Natural variant2381G → V in PFIC2. Ref.3
VAR_030388
Natural variant2841V → A Ref.5 Ref.9 Ref.11
VAR_035349
Natural variant2841V → L in PFIC2. Ref.5
VAR_013332
Natural variant2971E → G in PFIC2 and BRIC2; reduced transport capacity for taurocholate.
VAR_010271
Natural variant2991R → K: dbSNP rs2287617. Ref.9
VAR_030389
Natural variant3361C → S in PFIC2. Ref.3
VAR_030390
Natural variant4151R → Q Ref.7
VAR_043074
Natural variant4321R → T in BRIC2; reduced transport capacity for taurocholate. Ref.8
VAR_030391
Natural variant4441V → 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 variant4611K → E in PFIC2. Ref.1
VAR_013334
Natural variant4821D → G in PFIC2. Ref.1
VAR_013335
Natural variant5701A → T in BRIC2. Ref.6
VAR_030392
Natural variant5911N → S in a patient with intrahepatic cholestasis of pregnancy. Ref.7
VAR_043075
Natural variant6161R → G Ref.9
VAR_035350
Natural variant6191T → A Ref.9
VAR_035351
Natural variant6761D → Y in fluvastatin-induced cholestasis; does not affect transport capacity for taurocholate. Ref.11
VAR_043076
Natural variant6771M → V Does not affect transport capacity for taurocholate. dbSNP rs11568364. Ref.9 Ref.11 Ref.7 Ref.10
VAR_030393
Natural variant6981R → H Ref.9 Ref.11
VAR_035352
Natural variant8551G → R in ethinylestradiol/gestodene-induced cholestasis; loss of transport capacity for taurocholate. Ref.11
VAR_043077
Natural variant8651A → V Ref.9
VAR_035353
Natural variant9231T → P in BRIC2. Ref.6
VAR_030394
Natural variant9261A → P in BRIC2. Ref.6
VAR_030395
Natural variant9581R → Q Ref.9
VAR_035354
Natural variant9821G → R in PFIC2. Ref.1
VAR_013336
Natural variant10041G → D in PFIC2. Ref.5
VAR_013337
Natural variant10501R → C in BRIC2. Ref.6
VAR_030396
Natural variant11281R → H in BRIC2. Ref.6
VAR_030397
Natural variant11531R → C in PFIC2. Ref.1
VAR_013338
Natural variant11861E → K: dbSNP rs1521808.
VAR_030398
Natural variant12681R → Q in PFIC2. Ref.1
VAR_013339

Experimental info

Sequence conflict3391V → L in AAD28285. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O95342-1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: D444CACC48DEA371

FASTA1,321146,393
        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 

« Hide

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

Cross-references

Sequence databases

AF091582 mRNA. Translation: AAC77455.1.
AF136523 mRNA. Translation: AAD28285.1.
IPIIPI00184848.
RefSeqNP_003733.2.
UniGeneHs.658439

3D structure databases

HSSPHSSP built from PDB template 1MT0 based on UniProtKB P08716.
ModBaseSearch...

Protein family/group databases

TCDB3.A.1.201.2. ATP-binding cassette (ABC) superfamily.

PTM databases

PhosphoSiteO95342.

Proteomic databases

PRIDEO95342.

Genome annotation databases

EnsemblENSG00000073734. Homo sapiens. [Contig view]
GeneID8647.
KEGGhsa:8647.

Organism-specific databases

GeneCardsGC02M169487.
HGNCHGNC:42. ABCB11.
HPAHPA019035.
MIM601847. phenotype.
603201. gene.
605479. phenotype.
Orphanet172. Cholestasis, progressive familial intrahepatic.
79304. Cholestasis, progressive familial intrahepatic 2.
PharmGKBPA374.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO95342.
HOVERGENO95342.

Enzyme and pathway databases

ReactomeREACT_602. Lipid and lipoprotein metabolism.

Gene expression databases

ArrayExpressO95342.
BgeeO95342.
CleanExHS_ABCB11.
GermOnlineENSG00000073734. Homo sapiens.

Family and domain databases

InterProIPR001140. ABC_TM_transpt.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR017940. ABC_transporter_type1.
IPR003593. ATPase_AAA+_core.
[Graphical view]
PfamPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
ProDomPD000006. ABC_transporter. 2 hits.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00382. AAA. 2 hits.
[Graphical view]
PROSITEPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00171. Adenosine triphosphate.
DB00559. Bosentan.
DB01016. Glibenclamide.
NextBio32419.
SOURCESearch...

Entry information

Entry nameABCBB_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents