O95342 · ABCBB_HUMAN
- 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:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132).
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 + taurolithocholate 3-sulfate(in) = ADP + H+ + phosphate + taurolithocholate 3-sulfate(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 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, PubMed:32203132).
The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (PubMed:19228692).
The uptake of taurocholate is increased by short- and medium-chain fatty acids (PubMed:20398791).
Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (PubMed:24711118).
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, PubMed:32203132).
The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (PubMed:19228692).
The uptake of taurocholate is increased by short- and medium-chain fatty acids (PubMed:20398791).
Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (PubMed:24711118).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
30.4 μM | taurocholate | |||||
6.2 μM | taurocholate | |||||
21.7 μM | glycocholate | |||||
6.6 μM | taurochenodeoxycholate | |||||
7.5 μM | glycochenodeoxycholate | |||||
9.5 μM | taurolithocholate sulfate | |||||
4.61 μM | taurocholate | |||||
4.64 μM | taurocholate | |||||
124 μM | pravastatin | |||||
19.9 μM | taurocholate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
232 pmol/min/mg | for taurocholate transport | ||||
2510 pmol/min/mg | for taurocholate transport | ||||
2310 pmol/min/mg | for taurocholate transport | ||||
4290 pmol/min/mg | for taurocholate transport | ||||
1220 pmol/min/mg | for pravastatin transport | ||||
98.5 pmol/min/mg | for taurocholate transport |
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameBile salt export pump
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO95342
- Secondary accessions
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. Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway. Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (By similarity).
Cell membrane expression is up-regulated by short- and medium-chain fatty acids (PubMed:20398791).
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. Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway. Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (By similarity).
Cell membrane expression is up-regulated by short- and medium-chain fatty acids (PubMed:20398791).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-62 | Cytoplasmic | ||||
Sequence: MSDSVILRSIKKFGEENDGFESDKSYNNDKKSRLQDEKKGDGVRVGFFQLFRFSSSTDIWLM | ||||||
Transmembrane | 63-83 | Helical | ||||
Sequence: FVGSLCAFLHGIAQPGVLLIF | ||||||
Topological domain | 84-147 | Extracellular | ||||
Sequence: GTMTDVFIDYDVELQELQIPGKACVNNTIVWTNSSLNQNMTNGTRCGLLNIESEMIKFASYYAG | ||||||
Transmembrane | 148-168 | Helical | ||||
Sequence: IAVAVLITGYIQICFWVIAAA | ||||||
Topological domain | 169-215 | Cytoplasmic | ||||
Sequence: RQIQKMRKFYFRRIMRMEIGWFDCNSVGELNTRFSDDINKINDAIAD | ||||||
Transmembrane | 216-236 | Helical | ||||
Sequence: QMALFIQRMTSTICGFLLGFF | ||||||
Topological domain | 237-240 | Extracellular | ||||
Sequence: RGWK | ||||||
Transmembrane | 241-261 | Helical | ||||
Sequence: LTLVIISVSPLIGIGAATIGL | ||||||
Topological domain | 262-319 | Cytoplasmic | ||||
Sequence: SVSKFTDYELKAYAKAGVVADEVISSMRTVAAFGGEKREVERYEKNLVFAQRWGIRKG | ||||||
Transmembrane | 320-340 | Helical | ||||
Sequence: IVMGFFTGFVWCLIFLCYALA | ||||||
Topological domain | 341-353 | Extracellular | ||||
Sequence: FWYGSTLVLDEGE | ||||||
Transmembrane | 354-374 | Helical | ||||
Sequence: YTPGTLVQIFLSVIVGALNLG | ||||||
Topological domain | 375-755 | Cytoplasmic | ||||
Sequence: NASPCLEAFATGRAAATSIFETIDRKPIIDCMSEDGYKLDRIKGEIEFHNVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTALQLIQRFYDPCEGMVTVDGHDIRSLNIQWLRDQIGIVEQEPVLFSTTIAENIRYGREDATMEDIVQAAKEANAYNFIMDLPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEAMVQEVLSKIQHGHTIISVAHRLSTVRAADTIIGFEHGTAVERGTHEELLERKGVYFTLVTLQSQGNQALNEEDIKDATEDDMLARTFSRGSYQDSLRASIRQRSKSQLSYLVHEPPLAVVDHKSTYEEDRKDKDIPVQEEVEPAPVRRILKFSAPEWPYM | ||||||
Transmembrane | 756-776 | Helical | ||||
Sequence: LVGSVGAAVNGTVTPLYAFLF | ||||||
Topological domain | 777-794 | Extracellular | ||||
Sequence: SQILGTFSIPDKEEQRSQ | ||||||
Transmembrane | 795-815 | Helical | ||||
Sequence: INGVCLLFVAMGCVSLFTQFL | ||||||
Topological domain | 816-869 | Cytoplasmic | ||||
Sequence: QGYAFAKSGELLTKRLRKFGFRAMLGQDIAWFDDLRNSPGALTTRLATDASQVQ | ||||||
Transmembrane | 870-890 | Helical | ||||
Sequence: GAAGSQIGMIVNSFTNVTVAM | ||||||
Transmembrane | 891-911 | Helical | ||||
Sequence: IIAFSFSWKLSLVILCFFPFL | ||||||
Topological domain | 912-979 | Cytoplasmic | ||||
Sequence: ALSGATQTRMLTGFASRDKQALEMVGQITNEALSNIRTVAGIGKERRFIEALETELEKPFKTAIQKAN | ||||||
Transmembrane | 980-1000 | Helical | ||||
Sequence: IYGFCFAFAQCIMFIANSASY | ||||||
Topological domain | 1001-1011 | Extracellular | ||||
Sequence: RYGGYLISNEG | ||||||
Transmembrane | 1012-1032 | Helical | ||||
Sequence: LHFSYVFRVISAVVLSATALG | ||||||
Topological domain | 1033-1321 | Cytoplasmic | ||||
Sequence: RAFSYTPSYAKAKISAARFFQLLDRQPPISVYNTAGEKWDNFQGKIDFVDCKFTYPSRPDSQVLNGLSVSISPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGKVMIDGHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDNIKYGDNTKEIPMERVIAAAKQAQLHDFVMSLPEKYETNVGSQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQVALDKAREGRTCIVIAHRLSTIQNADIIAVMAQGVVIEKGTHEELMAQKGAYYKLVTTGSPIS |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Cholestasis, progressive familial intrahepatic, 2 (PFIC2)
- Note
- DescriptionA disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC2 inheritance is autosomal recessive.
- See alsoMIM:601847
Natural variants in PFIC2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_083783 | 129 | C>Y | in PFIC2; loss of cell membrane localization; significantly reduces taurocholate transport activity; dbSNP:rs1695246652 | |
VAR_030388 | 238 | G>V | in PFIC2; dbSNP:rs72551306 | |
VAR_013332 | 284 | V>L | in PFIC2 | |
VAR_010271 | 297 | E>G | in PFIC2 and BRIC2; reduces transport capacity for taurocholate; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; does not affect apical membrane localization; does not affect cell surface expression of the mature form; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect protein expression; does not affect cell membrane localization; dbSNP:rs11568372 | |
VAR_030390 | 336 | C>S | in PFIC2; dbSNP:rs72551305 | |
VAR_073967 | 337 | Y>H | in PFIC2; uncertain significance | |
VAR_013334 | 461 | K>E | in PFIC2; dbSNP:rs1274558905 | |
VAR_073968 | 472 | Y>C | in PFIC2; dbSNP:rs369860506 | |
VAR_013335 | 482 | D>G | in PFIC2; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; decreases apical membrane localization; affects cell surface expression; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; dbSNP:rs72549402 | |
VAR_073969 | 696 | R>W | in PFIC2; uncertain significance; dbSNP:rs376216286 | |
VAR_073970 | 931 | Q>P | in PFIC2; uncertain significance | |
VAR_013336 | 982 | G>R | in PFIC2; impairs taurocholate transport activity; significantly reduces protein expression; decreases cell surface protein expression; loss of ell membrane localization; dbSNP:rs72549399 | |
VAR_013337 | 1004 | G>D | in PFIC2 | |
VAR_073971 | 1131 | D>V | in PFIC2 | |
VAR_013338 | 1153 | R>C | in PFIC2; impairs taurocholate transport activity; significantly reduces protein expression; decreases cell surface protein expression; loss of ell membrane localization; dbSNP:rs72549395 | |
VAR_073972 | 1198 | H>R | in PFIC2; uncertain significance | |
VAR_013339 | 1268 | R>Q | in PFIC2; dbSNP:rs72549394 |
Cholestasis, benign recurrent intrahepatic, 2 (BRIC2)
- Note
- DescriptionA disorder 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. Patients are asymptomatic between episodes, both clinically and biochemically.
- See alsoMIM:605479
Natural variants in BRIC2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_030386 | 186 | E>G | in BRIC2; dbSNP:rs72551307 | |
VAR_010271 | 297 | E>G | in PFIC2 and BRIC2; reduces transport capacity for taurocholate; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; does not affect apical membrane localization; does not affect cell surface expression of the mature form; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect protein expression; does not affect cell membrane localization; dbSNP:rs11568372 | |
VAR_030391 | 432 | R>T | in BRIC2; reduced transport capacity for taurocholate; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; dbSNP:rs121908935 | |
VAR_030392 | 570 | A>T | in BRIC2; dbSNP:rs886043807 | |
VAR_030394 | 923 | T>P | in BRIC2; dbSNP:rs777469571 | |
VAR_030395 | 926 | A>P | in BRIC2; dbSNP:rs72549400 | |
VAR_030396 | 1050 | R>C | in BRIC2; dbSNP:rs72549398 | |
VAR_030397 | 1128 | R>H | in BRIC2; dbSNP:rs756220860 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1-441 | Does not affect ATPase-coupled bile acid transport activity. Decreases protein stability. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_055472 | 56 | does not affect taurocholate transport activity; does not affect cell surface protein expression; dbSNP:rs11568361 | |||
Sequence: S → L | ||||||
Natural variant | VAR_083783 | 129 | in PFIC2; loss of cell membrane localization; significantly reduces taurocholate transport activity; dbSNP:rs1695246652 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_030386 | 186 | in BRIC2; dbSNP:rs72551307 | |||
Sequence: E → G | ||||||
Natural variant | VAR_030387 | 206 | impairs taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; does not affect cell membrane localization; dbSNP:rs11568357 | |||
Sequence: I → V | ||||||
Natural variant | VAR_030388 | 238 | in PFIC2; dbSNP:rs72551306 | |||
Sequence: G → V | ||||||
Natural variant | VAR_035349 | 284 | in dbSNP:rs200739891 | |||
Sequence: V → A | ||||||
Natural variant | VAR_013332 | 284 | in PFIC2 | |||
Sequence: V → L | ||||||
Natural variant | VAR_010271 | 297 | in PFIC2 and BRIC2; reduces transport capacity for taurocholate; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; does not affect apical membrane localization; does not affect cell surface expression of the mature form; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect protein expression; does not affect cell membrane localization; dbSNP:rs11568372 | |||
Sequence: E → G | ||||||
Natural variant | VAR_030389 | 299 | in dbSNP:rs2287617 | |||
Sequence: R → K | ||||||
Natural variant | VAR_030390 | 336 | in PFIC2; dbSNP:rs72551305 | |||
Sequence: C → S | ||||||
Natural variant | VAR_073967 | 337 | in PFIC2; uncertain significance | |||
Sequence: Y → H | ||||||
Natural variant | VAR_043074 | 415 | in dbSNP:rs371656014 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_030391 | 432 | in BRIC2; reduced transport capacity for taurocholate; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; dbSNP:rs121908935 | |||
Sequence: R → T | ||||||
Natural variant | VAR_013333 | 444 | does not affect transport capacity for taurocholate; increases transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect cell surface protein expression; does not affect protein expression; dbSNP:rs2287622 | |||
Sequence: V → A | ||||||
Natural variant | VAR_059106 | 444 | in dbSNP:rs2287622 | |||
Sequence: V → D | ||||||
Natural variant | VAR_059107 | 444 | in dbSNP:rs2287622 | |||
Sequence: V → G | ||||||
Natural variant | VAR_013334 | 461 | in PFIC2; dbSNP:rs1274558905 | |||
Sequence: K → E | ||||||
Natural variant | VAR_073968 | 472 | in PFIC2; dbSNP:rs369860506 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_013335 | 482 | in PFIC2; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; decreases apical membrane localization; affects cell surface expression; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; dbSNP:rs72549402 | |||
Sequence: D → G | ||||||
Natural variant | VAR_083784 | 558 | impairs taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; does not affect cell membrane localization; dbSNP:rs11568369 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_030392 | 570 | in BRIC2; dbSNP:rs886043807 | |||
Sequence: A → T | ||||||
Natural variant | VAR_043075 | 591 | in a patient with intrahepatic cholestasis of pregnancy; impairs taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; does not affect cell membrane localization; dbSNP:rs11568367 | |||
Sequence: N → S | ||||||
Natural variant | VAR_083785 | 592 | does not affect taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; dbSNP:rs11568370 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_035350 | 616 | ||||
Sequence: R → G | ||||||
Natural variant | VAR_035351 | 619 | in dbSNP:rs912519986 | |||
Sequence: T → A | ||||||
Natural variant | VAR_043076 | 676 | in fluvastatin-induced cholestasis; does not affect transport capacity for taurocholate | |||
Sequence: D → Y | ||||||
Natural variant | VAR_030393 | 677 | does not affect taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; dbSNP:rs11568364 | |||
Sequence: M → V | ||||||
Natural variant | VAR_073969 | 696 | in PFIC2; uncertain significance; dbSNP:rs376216286 | |||
Sequence: R → W | ||||||
Natural variant | VAR_035352 | 698 | in dbSNP:rs138642043 | |||
Sequence: R → H | ||||||
Natural variant | VAR_043077 | 855 | in ethinylestradiol/gestodene-induced cholestasis; loss of transport capacity for taurocholate | |||
Sequence: G → R | ||||||
Natural variant | VAR_035353 | 865 | deacreases localization to the cell membrane; decreases the trafficking to the plasma membrane; dbSNP:rs118109635 | |||
Sequence: A → V | ||||||
Natural variant | VAR_030394 | 923 | in BRIC2; dbSNP:rs777469571 | |||
Sequence: T → P | ||||||
Natural variant | VAR_030395 | 926 | in BRIC2; dbSNP:rs72549400 | |||
Sequence: A → P | ||||||
Natural variant | VAR_073970 | 931 | in PFIC2; uncertain significance | |||
Sequence: Q → P | ||||||
Natural variant | VAR_035354 | 958 | in dbSNP:rs761363245 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_013336 | 982 | in PFIC2; impairs taurocholate transport activity; significantly reduces protein expression; decreases cell surface protein expression; loss of ell membrane localization; dbSNP:rs72549399 | |||
Sequence: G → R | ||||||
Natural variant | VAR_013337 | 1004 | in PFIC2 | |||
Sequence: G → D | ||||||
Natural variant | VAR_030396 | 1050 | in BRIC2; dbSNP:rs72549398 | |||
Sequence: R → C | ||||||
Natural variant | VAR_030397 | 1128 | in BRIC2; dbSNP:rs756220860 | |||
Sequence: R → H | ||||||
Natural variant | VAR_073971 | 1131 | in PFIC2 | |||
Sequence: D → V | ||||||
Natural variant | VAR_013338 | 1153 | in PFIC2; impairs taurocholate transport activity; significantly reduces protein expression; decreases cell surface protein expression; loss of ell membrane localization; dbSNP:rs72549395 | |||
Sequence: R → C | ||||||
Natural variant | VAR_030398 | 1186 | impairs taurocholate transport activity; does not affect protein expression; decreases cell surface protein expression; reduces plasma membrane localization; dbSNP:rs1521808 | |||
Sequence: E → K | ||||||
Natural variant | VAR_073972 | 1198 | in PFIC2; uncertain significance | |||
Sequence: H → R | ||||||
Natural variant | VAR_013339 | 1268 | in PFIC2; dbSNP:rs72549394 | |||
Sequence: R → Q | ||||||
Mutagenesis | 1311 | Loss of interaction with AP2A1 and AP2A2. Promotes ABCB11 plasma membrane trafficking. Does not affect plasma membrane localization. Inhibits ABCB11 internalization. | ||||
Sequence: Y → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,669 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000093296 | 1-1321 | Bile salt export pump | |||
Sequence: MSDSVILRSIKKFGEENDGFESDKSYNNDKKSRLQDEKKGDGVRVGFFQLFRFSSSTDIWLMFVGSLCAFLHGIAQPGVLLIFGTMTDVFIDYDVELQELQIPGKACVNNTIVWTNSSLNQNMTNGTRCGLLNIESEMIKFASYYAGIAVAVLITGYIQICFWVIAAARQIQKMRKFYFRRIMRMEIGWFDCNSVGELNTRFSDDINKINDAIADQMALFIQRMTSTICGFLLGFFRGWKLTLVIISVSPLIGIGAATIGLSVSKFTDYELKAYAKAGVVADEVISSMRTVAAFGGEKREVERYEKNLVFAQRWGIRKGIVMGFFTGFVWCLIFLCYALAFWYGSTLVLDEGEYTPGTLVQIFLSVIVGALNLGNASPCLEAFATGRAAATSIFETIDRKPIIDCMSEDGYKLDRIKGEIEFHNVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTALQLIQRFYDPCEGMVTVDGHDIRSLNIQWLRDQIGIVEQEPVLFSTTIAENIRYGREDATMEDIVQAAKEANAYNFIMDLPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEAMVQEVLSKIQHGHTIISVAHRLSTVRAADTIIGFEHGTAVERGTHEELLERKGVYFTLVTLQSQGNQALNEEDIKDATEDDMLARTFSRGSYQDSLRASIRQRSKSQLSYLVHEPPLAVVDHKSTYEEDRKDKDIPVQEEVEPAPVRRILKFSAPEWPYMLVGSVGAAVNGTVTPLYAFLFSQILGTFSIPDKEEQRSQINGVCLLFVAMGCVSLFTQFLQGYAFAKSGELLTKRLRKFGFRAMLGQDIAWFDDLRNSPGALTTRLATDASQVQGAAGSQIGMIVNSFTNVTVAMIIAFSFSWKLSLVILCFFPFLALSGATQTRMLTGFASRDKQALEMVGQITNEALSNIRTVAGIGKERRFIEALETELEKPFKTAIQKANIYGFCFAFAQCIMFIANSASYRYGGYLISNEGLHFSYVFRVISAVVLSATALGRAFSYTPSYAKAKISAARFFQLLDRQPPISVYNTAGEKWDNFQGKIDFVDCKFTYPSRPDSQVLNGLSVSISPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGKVMIDGHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDNIKYGDNTKEIPMERVIAAAKQAQLHDFVMSLPEKYETNVGSQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQVALDKAREGRTCIVIAHRLSTIQNADIIAVMAQGVVIEKGTHEELMAQKGAYYKLVTTGSPIS | ||||||
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 | 690 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 701 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 704 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1214 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1321 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
N-glycosylated.
Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11.
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with HAX1 (By similarity).
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 | O95342 | DDIT4L Q96D03 | 3 | EBI-3914067, EBI-742054 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 16-37 | Disordered | ||||
Sequence: ENDGFESDKSYNNDKKSRLQDE | ||||||
Domain | 62-385 | ABC transmembrane type-1 1 | ||||
Sequence: MFVGSLCAFLHGIAQPGVLLIFGTMTDVFIDYDVELQELQIPGKACVNNTIVWTNSSLNQNMTNGTRCGLLNIESEMIKFASYYAGIAVAVLITGYIQICFWVIAAARQIQKMRKFYFRRIMRMEIGWFDCNSVGELNTRFSDDINKINDAIADQMALFIQRMTSTICGFLLGFFRGWKLTLVIISVSPLIGIGAATIGLSVSKFTDYELKAYAKAGVVADEVISSMRTVAAFGGEKREVERYEKNLVFAQRWGIRKGIVMGFFTGFVWCLIFLCYALAFWYGSTLVLDEGEYTPGTLVQIFLSVIVGALNLGNASPCLEAFAT | ||||||
Domain | 420-656 | ABC transporter 1 | ||||
Sequence: IEFHNVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTALQLIQRFYDPCEGMVTVDGHDIRSLNIQWLRDQIGIVEQEPVLFSTTIAENIRYGREDATMEDIVQAAKEANAYNFIMDLPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEAMVQEVLSKIQHGHTIISVAHRLSTVRAADTIIGFEHGTAVERGTHEELLERKGVYFTLVTL | ||||||
Region | 651-672 | Interaction with HAX1 | ||||
Sequence: FTLVTLQSQGNQALNEEDIKDA | ||||||
Domain | 755-1043 | ABC transmembrane type-1 2 | ||||
Sequence: MLVGSVGAAVNGTVTPLYAFLFSQILGTFSIPDKEEQRSQINGVCLLFVAMGCVSLFTQFLQGYAFAKSGELLTKRLRKFGFRAMLGQDIAWFDDLRNSPGALTTRLATDASQVQGAAGSQIGMIVNSFTNVTVAMIIAFSFSWKLSLVILCFFPFLALSGATQTRMLTGFASRDKQALEMVGQITNEALSNIRTVAGIGKERRFIEALETELEKPFKTAIQKANIYGFCFAFAQCIMFIANSASYRYGGYLISNEGLHFSYVFRVISAVVLSATALGRAFSYTPSYAK | ||||||
Domain | 1078-1316 | ABC transporter 2 | ||||
Sequence: IDFVDCKFTYPSRPDSQVLNGLSVSISPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGKVMIDGHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDNIKYGDNTKEIPMERVIAAAKQAQLHDFVMSLPEKYETNVGSQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQVALDKAREGRTCIVIAHRLSTIQNADIIAVMAQGVVIEKGTHEELMAQKGAYYKLVTT | ||||||
Region | 1311-1314 | Mediates internalization from the plasma membrane | ||||
Sequence: YKLV |
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)146,407
- Last updated2009-11-03 v2
- Checksum61EE2173E2351D80
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H7C486 | H7C486_HUMAN | ABCB11 | 72 | ||
Q53S60 | Q53S60_HUMAN | ABCB11 | 451 | ||
A0A3B3IS78 | A0A3B3IS78_HUMAN | ABCB11 | 780 | ||
A0A3B3ISD4 | A0A3B3ISD4_HUMAN | ABCB11 | 101 | ||
A0A3B3ITV9 | A0A3B3ITV9_HUMAN | ABCB11 | 81 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 339 | in Ref. 1; AAC77455 | ||||
Sequence: L → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF091582 EMBL· GenBank· DDBJ | AAC77455.1 EMBL· GenBank· DDBJ | mRNA | ||
AF136523 EMBL· GenBank· DDBJ | AAD28285.1 EMBL· GenBank· DDBJ | mRNA | ||
AC008177 EMBL· GenBank· DDBJ | AAY24305.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC093723 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC069137 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |