O70127 · ABCBB_RAT
- ProteinBile salt export pump
- GeneAbcb11
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1321 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15901796, PubMed:16332456, PubMed:17082223, PubMed:18985798, PubMed:9545351).
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456).
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269).
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456).
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269).
Catalytic activity
- ATP + cholate(in) + H2O = ADP + cholate(out) + H+ + phosphateThis reaction proceeds in the forward direction.
CHEBI:30616 + cholate (in)CHEBI:29747+ CHEBI:15377 = CHEBI:456216 + cholate (out)CHEBI:29747+ CHEBI:15378 + CHEBI:43474 - ATP + H2O + taurocholate(in) = ADP + H+ + phosphate + taurocholate(out)This reaction proceeds in the forward direction.
- ATP + glycocholate(in) + H2O = ADP + glycocholate(out) + H+ + phosphateThis reaction proceeds in the forward direction.
- ATP + glycochenodeoxycholate(in) + H2O = ADP + glycochenodeoxycholate(out) + H+ + phosphateThis reaction proceeds in the forward direction.
- ATP + H2O + taurochenodeoxycholate(in) = ADP + H+ + phosphate + taurochenodeoxycholate(out)This reaction proceeds in the forward direction.
- ATP + glycoursodeoxycholate(in) + H2O = ADP + glycoursodeoxycholate(out) + H+ + phosphateThis reaction proceeds in the forward direction.
- ATP + H2O + tauroursodeoxycholate(in) = ADP + H+ + phosphate + tauroursodeoxycholate(out)This reaction proceeds in the forward direction.
- ATP + H2O + taurodeoxycholate(in) = ADP + H+ + phosphate + taurodeoxycholate(out)This reaction proceeds in the forward direction.
- ATP + H2O + pravastatin(in) = ADP + H+ + phosphate + pravastatin(out)This reaction proceeds in the forward direction.
Activity regulation
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC50 of 52.9 uM (PubMed:16332456).
Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:15901796, PubMed:18985798).
Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798).
The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity).
Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:15901796, PubMed:18985798).
Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798).
The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
9.7 μM | taurocholate | |||||
25.7 μM | glycocholate | |||||
10.2 μM | taurochenodeoxycholate | |||||
5.6 μM | glycochenodeoxycholate | |||||
22.2 μM | taurocholate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
2200 pmol/min/mg | for taurocholate transport | ||||
237 pmol/min/mg | for taurocholate transport |
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameBile salt export pump
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO70127
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Recycling endosome membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Note: Internalized at the canalicular membrane through interaction with the adapter protein complex 2 (AP-2) (PubMed:22262466).
At steady state, localizes in the canalicular membrane but is also present in recycling endosomes. ABCB11 constantly and rapidly exchanges between the two sites through tubulo-vesicles carriers that move along microtubules (PubMed:11113123, PubMed:15121884).
Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway (PubMed:11113123, PubMed:24643070).
Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (PubMed:11113123).
Cell membrane expression is up-regulated by short- and medium-chain fatty acids (By similarity).
At steady state, localizes in the canalicular membrane but is also present in recycling endosomes. ABCB11 constantly and rapidly exchanges between the two sites through tubulo-vesicles carriers that move along microtubules (PubMed:11113123, PubMed:15121884).
Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway (PubMed:11113123, PubMed:24643070).
Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (PubMed:11113123).
Cell membrane expression is up-regulated by short- and medium-chain fatty acids (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-62 | Cytoplasmic | ||||
Sequence: MSDSVILRSVKKFGEENHAFESDGSHNNDKKSRLQDKMKEGDIRVGFFELFRFSSSKDIWLM | ||||||
Transmembrane | 63-83 | Helical | ||||
Sequence: LMGGVCALLHGMAQPGILIIF | ||||||
Topological domain | 84-147 | Extracellular | ||||
Sequence: GIMTDIFIKYDIERQELEIPGKACVNNTIVWINSSFHQNMTNGTVCGLVDIESEMIKFSGIYAG | ||||||
Transmembrane | 148-168 | Helical | ||||
Sequence: VGMTVLILGYFQIRLWVITGA | ||||||
Topological domain | 169-215 | Cytoplasmic | ||||
Sequence: RQIRRMRKIYFRRIMRMEIGWFDCTSVGELNSRFADDIEKINDAIAD | ||||||
Transmembrane | 216-236 | Helical | ||||
Sequence: QLAHFLQRMSTAMCGLLLGFY | ||||||
Topological domain | 237-240 | Extracellular | ||||
Sequence: RGWK | ||||||
Transmembrane | 241-261 | Helical | ||||
Sequence: LTLVILAVSPLIGIGAAVIGL | ||||||
Topological domain | 262-319 | Cytoplasmic | ||||
Sequence: SIAKFTELELKAYAKAGSIADEVLSSIRTVAAFGGENKEVERYEKNLVFAQRWGIWKG | ||||||
Transmembrane | 320-340 | Helical | ||||
Sequence: MVMGFFTGYMWCLIFFCYALA | ||||||
Topological domain | 341-353 | Extracellular | ||||
Sequence: FWYGSTLVLDEEE | ||||||
Transmembrane | 354-374 | Helical | ||||
Sequence: YTPGTLVQIFLCVILAAMNIG | ||||||
Topological domain | 375-755 | Cytoplasmic | ||||
Sequence: HASSCLEIFSTGCSAATNIFQTIDRQPVIDCMSGDGYKLDRIKGEIEFHNVTFHYPSRPDVKILDNLSMVIKPGETTALVGSSGAGKSTALQLIQRFYDPCEGMVTLDGHDIRSLNIRWLRDQIGIVEQEPVLFSTTIAENIRFGREDATMEDIVQAAKDANAYNFIMALPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEARVQEALNKIQHGHTIISVAHRLSTVRAADVIIGFEHGVAVERGTHEELLERKGVYFMLVTLQSQGDNAHKETSIMGKDATEGGTLERTFSRGSYRDSLRASIRQRSKSQLSLLTHDPPLAVADHKSSYKDSKDNDVLVEEVEPAPVRRILKYNIPEWHYI | ||||||
Transmembrane | 756-776 | Helical | ||||
Sequence: LVGSLSAAINGAVTPIYSLLF | ||||||
Topological domain | 777-794 | Extracellular | ||||
Sequence: SQLLGTFSLLDKEQQRSE | ||||||
Transmembrane | 795-815 | Helical | ||||
Sequence: IHSMCLFFVILGCVSIFTQFL | ||||||
Topological domain | 816-869 | Cytoplasmic | ||||
Sequence: QGYTFAKSGELLTKRLRKFGFKAMLGQDIGWFDDLRNNPGVLTTRLATDASQVQ | ||||||
Transmembrane | 870-890 | Helical | ||||
Sequence: GATGSQVGMMVNSFTNIIAAL | ||||||
Transmembrane | 891-911 | Helical | ||||
Sequence: LIAFFFSWKLSLIITIFFPFL | ||||||
Topological domain | 912-979 | Cytoplasmic | ||||
Sequence: ALSGAVQTKMLTGFASQDKQALEKAGQITSEALSNIRTVAGIGVEGRFIKAFEVELQTSYKTAVRKAN | ||||||
Transmembrane | 980-1000 | Helical | ||||
Sequence: IYGLCFAFSQGIAFLANSAAY | ||||||
Topological domain | 1001-1011 | Extracellular | ||||
Sequence: RYGGYLIAYEG | ||||||
Transmembrane | 1012-1032 | Helical | ||||
Sequence: LGFSHVFRVVSSVALSATAVG | ||||||
Topological domain | 1033-1321 | Cytoplasmic | ||||
Sequence: RTFSYTPSYAKAKISAARFFQLLDRKPPINVYSEAGEKWDNFQGKIDFIDCKFTYPSRPDIQVLNGLSVSVNPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGTVMIDGHDSKKVNIQFLRSNIGIVSQEPVLFDCSIMDNIKYGDNTKEISVERAIAAAKQAQLHDFVMSLPEKYETNVGIQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQTALDKAREGRTCIVIAHRLSTIQNSDIIAVVSQGVVIEKGTHEKLMAQKGAYYKLVITGAPIS |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 109 | Impairs N-glycosylation; when associated with Q-116; Q-122 and Q-125. Significantly decreases taurocholate; when associated with Q-116; Q-122 and Q-125. Significantly decreases protein expression; when associated with Q-116; Q-122 and Q-125. Affects protein localization at the apical membrane; when associated with Q-116; Q-122 and Q-125. Does not affect protein localization at the apical membrane. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 116 | Impairs N-glycosylation; when associated with Q-109; Q-122 and Q-125. Significantly decreases taurocholate; when associated with Q-109; Q-122 and Q-125. Significantly decreases protein expression; when associated with Q-109; Q-122 and Q-125. Affects protein localization at the apical membrane; when associated with Q-109; Q-122 and Q-125. Does not affect protein localization at the apical membrane; when associated with Q-109; Q-122 and Q-125. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 122 | Impairs N-glycosylation; when associated with Q-109; Q-116 and Q-125. Significantly decreases taurocholate; when associated with Q-109; Q-116 and Q-125. Significantly decreases protein expression; when associated with Q-109; Q-116 and Q-125. Affects protein localization at the apical membrane; when associated with Q-109; Q-116 and Q-125. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 125 | Impairs N-glycosylation; when associated with Q-109; Q-116 and Q-122. Significantly decreases taurocholate; when associated with Q-109; Q-116 and Q-122. Significantly decreases protein expression; when associated with Q-109; Q-116 and Q-122. Affects protein localization at the apical membrane;when associated with Q-109; Q-116 and Q-122. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 1311 | Deacreases ABCB11 internalization. | ||||
Sequence: Y → A |
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000093299 | 1-1321 | Bile salt export pump | |||
Sequence: MSDSVILRSVKKFGEENHAFESDGSHNNDKKSRLQDKMKEGDIRVGFFELFRFSSSKDIWLMLMGGVCALLHGMAQPGILIIFGIMTDIFIKYDIERQELEIPGKACVNNTIVWINSSFHQNMTNGTVCGLVDIESEMIKFSGIYAGVGMTVLILGYFQIRLWVITGARQIRRMRKIYFRRIMRMEIGWFDCTSVGELNSRFADDIEKINDAIADQLAHFLQRMSTAMCGLLLGFYRGWKLTLVILAVSPLIGIGAAVIGLSIAKFTELELKAYAKAGSIADEVLSSIRTVAAFGGENKEVERYEKNLVFAQRWGIWKGMVMGFFTGYMWCLIFFCYALAFWYGSTLVLDEEEYTPGTLVQIFLCVILAAMNIGHASSCLEIFSTGCSAATNIFQTIDRQPVIDCMSGDGYKLDRIKGEIEFHNVTFHYPSRPDVKILDNLSMVIKPGETTALVGSSGAGKSTALQLIQRFYDPCEGMVTLDGHDIRSLNIRWLRDQIGIVEQEPVLFSTTIAENIRFGREDATMEDIVQAAKDANAYNFIMALPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEARVQEALNKIQHGHTIISVAHRLSTVRAADVIIGFEHGVAVERGTHEELLERKGVYFMLVTLQSQGDNAHKETSIMGKDATEGGTLERTFSRGSYRDSLRASIRQRSKSQLSLLTHDPPLAVADHKSSYKDSKDNDVLVEEVEPAPVRRILKYNIPEWHYILVGSLSAAINGAVTPIYSLLFSQLLGTFSLLDKEQQRSEIHSMCLFFVILGCVSIFTQFLQGYTFAKSGELLTKRLRKFGFKAMLGQDIGWFDDLRNNPGVLTTRLATDASQVQGATGSQVGMMVNSFTNIIAALLIAFFFSWKLSLIITIFFPFLALSGAVQTKMLTGFASQDKQALEKAGQITSEALSNIRTVAGIGVEGRFIKAFEVELQTSYKTAVRKANIYGLCFAFSQGIAFLANSAAYRYGGYLIAYEGLGFSHVFRVVSSVALSATAVGRTFSYTPSYAKAKISAARFFQLLDRKPPINVYSEAGEKWDNFQGKIDFIDCKFTYPSRPDIQVLNGLSVSVNPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGTVMIDGHDSKKVNIQFLRSNIGIVSQEPVLFDCSIMDNIKYGDNTKEISVERAIAAAKQAQLHDFVMSLPEKYETNVGIQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQTALDKAREGRTCIVIAHRLSTIQNSDIIAVVSQGVVIEKGTHEKLMAQKGAYYKLVITGAPIS | ||||||
Glycosylation | 109 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 116 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 122 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 125 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 586 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 587 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 692 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 703 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 706 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1321 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11.
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Interaction
Subunit
Interacts with HAX1 (PubMed:15159385).
Interacts with the adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (PubMed:22262466).
Interacts with the adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (PubMed:22262466).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O70127 | Hax1 Q7TSE9 | 5 | EBI-930036, EBI-930005 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 62-385 | ABC transmembrane type-1 1 | ||||
Sequence: MLMGGVCALLHGMAQPGILIIFGIMTDIFIKYDIERQELEIPGKACVNNTIVWINSSFHQNMTNGTVCGLVDIESEMIKFSGIYAGVGMTVLILGYFQIRLWVITGARQIRRMRKIYFRRIMRMEIGWFDCTSVGELNSRFADDIEKINDAIADQLAHFLQRMSTAMCGLLLGFYRGWKLTLVILAVSPLIGIGAAVIGLSIAKFTELELKAYAKAGSIADEVLSSIRTVAAFGGENKEVERYEKNLVFAQRWGIWKGMVMGFFTGYMWCLIFFCYALAFWYGSTLVLDEEEYTPGTLVQIFLCVILAAMNIGHASSCLEIFST | ||||||
Domain | 420-656 | ABC transporter 1 | ||||
Sequence: IEFHNVTFHYPSRPDVKILDNLSMVIKPGETTALVGSSGAGKSTALQLIQRFYDPCEGMVTLDGHDIRSLNIRWLRDQIGIVEQEPVLFSTTIAENIRFGREDATMEDIVQAAKDANAYNFIMALPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEARVQEALNKIQHGHTIISVAHRLSTVRAADVIIGFEHGVAVERGTHEELLERKGVYFMLVTL | ||||||
Region | 651-674 | Interaction with HAX1 | ||||
Sequence: FMLVTLQSQGDNAHKETSIMGKDA | ||||||
Domain | 755-1043 | ABC transmembrane type-1 2 | ||||
Sequence: ILVGSLSAAINGAVTPIYSLLFSQLLGTFSLLDKEQQRSEIHSMCLFFVILGCVSIFTQFLQGYTFAKSGELLTKRLRKFGFKAMLGQDIGWFDDLRNNPGVLTTRLATDASQVQGATGSQVGMMVNSFTNIIAALLIAFFFSWKLSLIITIFFPFLALSGAVQTKMLTGFASQDKQALEKAGQITSEALSNIRTVAGIGVEGRFIKAFEVELQTSYKTAVRKANIYGLCFAFSQGIAFLANSAAYRYGGYLIAYEGLGFSHVFRVVSSVALSATAVGRTFSYTPSYAK | ||||||
Domain | 1078-1316 | ABC transporter 2 | ||||
Sequence: IDFIDCKFTYPSRPDIQVLNGLSVSVNPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGTVMIDGHDSKKVNIQFLRSNIGIVSQEPVLFDCSIMDNIKYGDNTKEISVERAIAAAKQAQLHDFVMSLPEKYETNVGIQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQTALDKAREGRTCIVIAHRLSTIQNSDIIAVVSQGVVIEKGTHEKLMAQKGAYYKLVIT |
Domain
Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
Sequence similarities
Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,321
- Mass (Da)146,258
- Last updated1998-08-01 v1
- Checksum5443F4EF7B9FB1F6
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M0R4J2 | M0R4J2_RAT | Abcb11 | 1320 | ||
A0A8I5ZYZ3 | A0A8I5ZYZ3_RAT | Abcb11 | 1300 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U69487 EMBL· GenBank· DDBJ | AAC40084.1 EMBL· GenBank· DDBJ | mRNA |