Human Gene ABCB11 (uc010zdb.1) Description and Page Index
  Description: Homo sapiens ATP-binding cassette, sub-family B (MDR/TAP), member 11 (ABCB11), mRNA.
RefSeq Summary (NM_003742): The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF091582.1, AF136523.1 [ECO:0000332] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr2:169,779,449-169,828,571 Size: 49,123 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg19 chr2:169,780,132-169,828,422 Size: 48,291 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:169,779,449-169,828,571)mRNA (may differ from genome)Protein (797 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: ABCBB_HUMAN
DESCRIPTION: RecName: Full=Bile salt export pump; AltName: Full=ATP-binding cassette sub-family B member 11;
FUNCTION: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=30.4 uM for taurocholate; Vmax=232 pmol/min/mg enzyme for taurocholate transport;
SUBUNIT: Interacts with HAX1 (By similarity).
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.
DOMAIN: Multifunctional polypeptide with two homologous halves, each containing an hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
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.
DISEASE: 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.
SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
SIMILARITY: Contains 2 ABC transmembrane type-1 domains.
SIMILARITY: Contains 2 ABC transporter domains.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ABCB11";
WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=O95342";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ABCB11
CDC HuGE Published Literature: ABCB11
Positive Disease Associations: Alkaline Phosphatase , cholestasis , cholestasis, drug-induced hepatotoxicity , Echocardiography , fasting plasma glucose , Glucose , Hemoglobin A, Glycosylated , Hip , Metabolic Syndrome X , other metabolic traits , plasma glucose, basal hepatic glucose and increased insulin release
Related Studies:
  1. Alkaline Phosphatase
    John C Chambers et al. Nature genetics 2011, Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma., Nature genetics. [PubMed 22001757]
  2. cholestasis
    Eloranta, M. L. et al. 2003, Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy., Scandinavian journal of gastroenterology. 2003 Jun;38(6):648-52. [PubMed 12825874]
    The use of two intragenic SNPs in both single locus and haplotype analyses of association suggests that the BSEP gene is a susceptibility gene in intrahepatic cholestasis of pregnancy.
  3. cholestasis, drug-induced hepatotoxicity
    Lang, C. et al. 2007, Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury, Pharmacogenet Genomics 2007 17(1) 47-60. [PubMed 17264802]
    In summary, our data support a role of ABCB11 and ABCB4 mutations and polymorphisms in drug-induced cholestasis. Genotyping of selected patients with acquired cholestasis might help to identify individuals with a genetic predisposition.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: ABCB11
Diseases sorted by gene-association score: cholestasis, progressive familial intrahepatic 2* (1593), cholestasis, benign recurrent intrahepatic, 2* (1581), intrahepatic cholestasis* (474), abcb11-related intrahepatic cholestasis* (200), cholestasis (49), cholestasis, benign recurrent intrahepatic (28), liver disease (18), bile duct disease (14), atp8b1 deficiency (12), cholestasis, progressive familial intrahepatic 3 (12), colchicine resistance (11), cholestasis, progressive familial intrahepatic 1 (9), biliary tract disease (9), sclerosing cholangitis (6), biliary atresia (5), cholangitis (5), alagille syndrome 1 (4), hereditary spherocytosis (2), gastrointestinal system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.54 RPKM in Liver
Total median expression: 11.54 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -39.20149-0.263 Picture PostScript Text
3' UTR -207.40683-0.304 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003593 - AAA+_ATPase
IPR003439 - ABC_transporter-like
IPR017871 - ABC_transporter_CS
IPR017940 - ABC_transporter_type1
IPR001140 - ABC_transptr_TM_dom
IPR011527 - ABC_transptrTM_dom_typ1

Pfam Domains:
PF00005 - ABC transporter
PF00664 - ABC transporter transmembrane region

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases
53795 - PEP carboxykinase-like
90123 - Multidrug resistance ABC transporter MsbA, N-terminal domain

ModBase Predicted Comparative 3D Structure on O95342
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005215 transporter activity
GO:0005524 ATP binding
GO:0008554 sodium-exporting ATPase activity, phosphorylative mechanism
GO:0015126 canalicular bile acid transmembrane transporter activity
GO:0015432 bile acid-exporting ATPase activity
GO:0016887 ATPase activity
GO:0042626 ATPase activity, coupled to transmembrane movement of substances

Biological Process:
GO:0006699 bile acid biosynthetic process
GO:0015721 bile acid and bile salt transport
GO:0015722 canalicular bile acid transport
GO:0035725 sodium ion transmembrane transport
GO:0055085 transmembrane transport
GO:0099132 ATP hydrolysis coupled cation transmembrane transport

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0045177 apical part of cell
GO:0046581 intercellular canaliculus
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AF091582 - Homo sapiens bile salt export pump (BSEP) mRNA, complete cds.
AF136523 - Homo sapiens bile salt export pump (BSEP) mRNA, complete cds.
JD479511 - Sequence 460535 from Patent EP1572962.
JD342734 - Sequence 323758 from Patent EP1572962.
JD362668 - Sequence 343692 from Patent EP1572962.
JD487116 - Sequence 468140 from Patent EP1572962.
JD524062 - Sequence 505086 from Patent EP1572962.
JD504606 - Sequence 485630 from Patent EP1572962.
JD142623 - Sequence 123647 from Patent EP1572962.
AK302540 - Homo sapiens cDNA FLJ56177 complete cds, highly similar to Bile salt export pump.
JD483126 - Sequence 464150 from Patent EP1572962.
JD325131 - Sequence 306155 from Patent EP1572962.
JD435393 - Sequence 416417 from Patent EP1572962.
JD371058 - Sequence 352082 from Patent EP1572962.
JD089990 - Sequence 71014 from Patent EP1572962.
JD037681 - Sequence 18705 from Patent EP1572962.
AK303050 - Homo sapiens cDNA FLJ51418 complete cds, highly similar to Bile salt export pump.
JD171661 - Sequence 152685 from Patent EP1572962.
BC172890 - Synthetic construct Homo sapiens clone IMAGE:9094466 ATP-binding cassette, sub-family B (MDR/TAP), member 11 (ABCB11) gene, partial cds.
AB012959 - Homo sapiens mRNA for sister p-glycoprotein, partial cds.
BC172889 - Synthetic construct Homo sapiens clone IMAGE:9094465 ATP-binding cassette, sub-family B (MDR/TAP), member 11 (ABCB11) gene, partial cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa02010 - ABC transporters

BioCarta from NCI Cancer Genome Anatomy Project
h_mrpPathway - Multi-Drug Resistance Factors
h_nuclearRsPathway - Nuclear Receptors in Lipid Metabolism and Toxicity

Reactome (by CSHL, EBI, and GO)

Protein O95342 (Reactome details) participates in the following event(s):

R-HSA-193362 ABCB11 transports bile salts from cytosol to extracellular region
R-HSA-159418 Recycling of bile acids and salts
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-194068 Bile acid and bile salt metabolism
R-HSA-192105 Synthesis of bile acids and bile salts
R-HSA-8957322 Metabolism of steroids
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ABCBB_HUMAN, AK302540, BSEP, NM_003742, NP_003733, O95342, Q53TL2, Q9UNB2
UCSC ID: uc010zdb.1
RefSeq Accession: NM_003742
Protein: O95342 (aka ABCBB_HUMAN or AB11_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AK302540.1
exon count: 15CDS single in 3' UTR: no RNA size: 2968
ORF size: 2394CDS single in intron: no Alignment % ID: 99.83
txCdsPredict score: 4555.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 11# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.