P21440 · MDR3_MOUSE
- ProteinPhosphatidylcholine translocator ABCB4
- GeneAbcb4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1276 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi between hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:7592705, PubMed:7814632, PubMed:7912658, PubMed:8106172, PubMed:8725158, PubMed:9366571).
Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (By similarity).
Required for proper phospholipid bile formation (PubMed:8106172).
Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:7814632, PubMed:8725158).
May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571).
In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390).
Does not confer multidrug resistance (PubMed:1990275).
Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (By similarity).
Required for proper phospholipid bile formation (PubMed:8106172).
Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:7814632, PubMed:8725158).
May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571).
In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390).
Does not confer multidrug resistance (PubMed:1990275).
Catalytic activity
- a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + H+ + phosphateThis reaction proceeds in the forward direction.
- a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + H+ + phosphateThis reaction proceeds in the forward direction.
- a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Activity regulation
Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:7912658).
Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705).
Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 403 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 429-434 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: GCGKST | ||||||
Binding site | 474 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 533 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 1043 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1068-1074 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: SGCGKST | ||||||
Binding site | 1114 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 1174-1176 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: GGQ |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended namePhosphatidylcholine translocator ABCB4
- 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 > Mus > Mus
Accessions
- Primary accessionP21440
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Note: Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner. Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner (By similarity).
Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (PubMed:1381362, PubMed:8106172, PubMed:8615769).
Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132).
Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (PubMed:1381362, PubMed:8106172, PubMed:8615769).
Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-47 | Cytoplasmic | ||||
Sequence: MDLEAARNGTARRLDGDFELGSISNQGREKKKKVNLIGLLTLFRYSD | ||||||
Transmembrane | 48-70 | Helical | ||||
Sequence: WQDKLFMFLGTLMAIAHGSGLPL | ||||||
Topological domain | 71-115 | Extracellular | ||||
Sequence: MMIVFGEMTDKFVDNTGNFSLPVNFSLSMLNPGRILEEEMTRYAY | ||||||
Transmembrane | 116-136 | Helical | ||||
Sequence: YYSGLGGGVLVAAYIQVSFWT | ||||||
Topological domain | 137-185 | Cytoplasmic | ||||
Sequence: LAAGRQIKKIRQKFFHAILRQEMGWFDIKGTTELNTRLTDDVSKISEGI | ||||||
Transmembrane | 186-207 | Helical | ||||
Sequence: GDKVGMFFQAIATFFAGFIVGF | ||||||
Topological domain | 208-212 | Extracellular | ||||
Sequence: IRGWK | ||||||
Transmembrane | 213-235 | Helical | ||||
Sequence: LTLVIMAISPILGLSTAVWAKIL | ||||||
Topological domain | 236-293 | Cytoplasmic | ||||
Sequence: STFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKKIGIKKAIS | ||||||
Transmembrane | 294-315 | Helical | ||||
Sequence: ANISMGIAFLLIYASYALAFWY | ||||||
Topological domain | 316-329 | Extracellular | ||||
Sequence: GSTLVISKEYTIGN | ||||||
Transmembrane | 330-351 | Helical | ||||
Sequence: AMTVFFSILIGAFSVGQAAPCI | ||||||
Topological domain | 352-708 | Cytoplasmic | ||||
Sequence: DAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDNIKGNLEFSDVHFSYPSRANIKILKGLNLKVKSGQTVALVGNSGCGKSTTVQLLQRLYDPTEGKISIDGQDIRNFNVRCLREIIGVVSQEPVLFSTTIAENIRYGRGNVTMDEIEKAVKEANAYDFIMKLPQKFDTLVGDRGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTIRNADVIAGFEDGVIVEQGSHSELMKKEGIYFRLVNMQTAGSQILSEEFEVELSDEKAAGDVAPNGWKARIFRNSTKKSLKSPHQNRLDEETNELDANVPPVSFLKVLKLNKTEWPYF | ||||||
Transmembrane | 709-729 | Helical | ||||
Sequence: VVGTVCAIANGALQPAFSIIL | ||||||
Topological domain | 730-752 | Extracellular | ||||
Sequence: SEMIAIFGPGDDAVKQQKCNMFS | ||||||
Transmembrane | 753-773 | Helical | ||||
Sequence: LVFLGLGVLSFFTFFLQGFTF | ||||||
Topological domain | 774-828 | Cytoplasmic | ||||
Sequence: GKAGEILTTRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTR | ||||||
Transmembrane | 829-849 | Helical | ||||
Sequence: LALIAQNTANLGTGIIISFIY | ||||||
Topological domain | 850 | Extracellular | ||||
Sequence: G | ||||||
Transmembrane | 851-870 | Helical | ||||
Sequence: WQLTLLLLSVVPFIAVAGIV | ||||||
Topological domain | 871-930 | Cytoplasmic | ||||
Sequence: EMKMLAGNAKRDKKEMEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLHGPYRNSVRK | ||||||
Transmembrane | 931-953 | Helical | ||||
Sequence: AHIYGITFSISQAFMYFSYAGCF | ||||||
Topological domain | 954-969 | Extracellular | ||||
Sequence: RFGSYLIVNGHMRFKD | ||||||
Transmembrane | 970-991 | Helical | ||||
Sequence: VILVFSAIVLGAVALGHASSFA | ||||||
Topological domain | 992-1276 | Cytoplasmic | ||||
Sequence: PDYAKAKLSAAYLFSLFERQPLIDSYSGEGLWPDKFEGSVTFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPMAGSVLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVPHDEIVRAAKEANIHPFIETLPQKYNTRVGDKGTQLSGGQKQRIAIARALIRQPRVLLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVIENGKVKEHGTHQQLLAQKGIYFSMVNIQAGTQNL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice show severe necrotic damage of hepatocytes, strong portal inflammation, proliferation and destruction of the canalicular and small bile ductular tracts (PubMed:8106172).
Display almost complete reduction of biliary phospholipid secretion, although bile salt secretion is normal (PubMed:7814632, PubMed:8106172, PubMed:8725158, PubMed:9366571).
Show also reduced cholesterol secretion (PubMed:8106172, PubMed:9366571).
Knockout mice lacking both ABCB4 and ATP8B1 show lower hepatic damage compared with the single ABCB4 knockout mice (PubMed:21820390).
Display equivalent reduction of biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout mice (PubMed:21820390).
Biliary cholesterol secretion is higher compared to the single ABCB4 knockout mice (PubMed:21820390).
Bile salt secretion is normal in both single ABCB4 knockout mice and double ABCB4 and ATP8B1 knockout mice (PubMed:21820390).
Biliary excretion of canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is strongly reduced compared to single ATP8B1 knockout mice (PubMed:21820390).
Display almost complete reduction of biliary phospholipid secretion, although bile salt secretion is normal (PubMed:7814632, PubMed:8106172, PubMed:8725158, PubMed:9366571).
Show also reduced cholesterol secretion (PubMed:8106172, PubMed:9366571).
Knockout mice lacking both ABCB4 and ATP8B1 show lower hepatic damage compared with the single ABCB4 knockout mice (PubMed:21820390).
Display equivalent reduction of biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout mice (PubMed:21820390).
Biliary cholesterol secretion is higher compared to the single ABCB4 knockout mice (PubMed:21820390).
Bile salt secretion is normal in both single ABCB4 knockout mice and double ABCB4 and ATP8B1 knockout mice (PubMed:21820390).
Biliary excretion of canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is strongly reduced compared to single ATP8B1 knockout mice (PubMed:21820390).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 50 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000093337 | 1-1276 | Phosphatidylcholine translocator ABCB4 | |||
Sequence: MDLEAARNGTARRLDGDFELGSISNQGREKKKKVNLIGLLTLFRYSDWQDKLFMFLGTLMAIAHGSGLPLMMIVFGEMTDKFVDNTGNFSLPVNFSLSMLNPGRILEEEMTRYAYYYSGLGGGVLVAAYIQVSFWTLAAGRQIKKIRQKFFHAILRQEMGWFDIKGTTELNTRLTDDVSKISEGIGDKVGMFFQAIATFFAGFIVGFIRGWKLTLVIMAISPILGLSTAVWAKILSTFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKKIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDNIKGNLEFSDVHFSYPSRANIKILKGLNLKVKSGQTVALVGNSGCGKSTTVQLLQRLYDPTEGKISIDGQDIRNFNVRCLREIIGVVSQEPVLFSTTIAENIRYGRGNVTMDEIEKAVKEANAYDFIMKLPQKFDTLVGDRGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTIRNADVIAGFEDGVIVEQGSHSELMKKEGIYFRLVNMQTAGSQILSEEFEVELSDEKAAGDVAPNGWKARIFRNSTKKSLKSPHQNRLDEETNELDANVPPVSFLKVLKLNKTEWPYFVVGTVCAIANGALQPAFSIILSEMIAIFGPGDDAVKQQKCNMFSLVFLGLGVLSFFTFFLQGFTFGKAGEILTTRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNTANLGTGIIISFIYGWQLTLLLLSVVPFIAVAGIVEMKMLAGNAKRDKKEMEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLHGPYRNSVRKAHIYGITFSISQAFMYFSYAGCFRFGSYLIVNGHMRFKDVILVFSAIVLGAVALGHASSFAPDYAKAKLSAAYLFSLFERQPLIDSYSGEGLWPDKFEGSVTFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPMAGSVLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVPHDEIVRAAKEANIHPFIETLPQKYNTRVGDKGTQLSGGQKQRIAIARALIRQPRVLLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVIENGKVKEHGTHQQLLAQKGIYFSMVNIQAGTQNL | ||||||
Modified residue | 24 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 88 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 94 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Phosphorylated. Phosphorylation is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner. May be phosphorylated on Thr-41 and Ser-46.
Glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the liver (PubMed:1381362, PubMed:8615769) (at protein level). Expressed in adrenal, liver, muscle, spleen and heart (PubMed:2471060).
Expressed in multidrug-resistant cell lines (PubMed:1969609).
Expressed in multidrug-resistant cell lines (PubMed:1969609).
Induction
Up-regulated by compounds that cause peroxisome proliferation, such as ciprofibrate and clofibrate (at protein level) (PubMed:8615769).
Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, ciprofibrate, clofibrate, bezafibrate and gemfibrozil (PubMed:12381268, PubMed:8615769).
Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, ciprofibrate, clofibrate, bezafibrate and gemfibrozil (PubMed:12381268, PubMed:8615769).
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 54-356 | ABC transmembrane type-1 1 | ||||
Sequence: MFLGTLMAIAHGSGLPLMMIVFGEMTDKFVDNTGNFSLPVNFSLSMLNPGRILEEEMTRYAYYYSGLGGGVLVAAYIQVSFWTLAAGRQIKKIRQKFFHAILRQEMGWFDIKGTTELNTRLTDDVSKISEGIGDKVGMFFQAIATFFAGFIVGFIRGWKLTLVIMAISPILGLSTAVWAKILSTFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKKIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFAN | ||||||
Domain | 391-627 | ABC transporter 1 | ||||
Sequence: LEFSDVHFSYPSRANIKILKGLNLKVKSGQTVALVGNSGCGKSTTVQLLQRLYDPTEGKISIDGQDIRNFNVRCLREIIGVVSQEPVLFSTTIAENIRYGRGNVTMDEIEKAVKEANAYDFIMKLPQKFDTLVGDRGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTIRNADVIAGFEDGVIVEQGSHSELMKKEGIYFRLVNM | ||||||
Region | 622-646 | Interaction with HAX1 | ||||
Sequence: FRLVNMQTAGSQILSEEFEVELSDE | ||||||
Domain | 708-996 | ABC transmembrane type-1 2 | ||||
Sequence: FVVGTVCAIANGALQPAFSIILSEMIAIFGPGDDAVKQQKCNMFSLVFLGLGVLSFFTFFLQGFTFGKAGEILTTRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNTANLGTGIIISFIYGWQLTLLLLSVVPFIAVAGIVEMKMLAGNAKRDKKEMEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLHGPYRNSVRKAHIYGITFSISQAFMYFSYAGCFRFGSYLIVNGHMRFKDVILVFSAIVLGAVALGHASSFAPDYAK | ||||||
Domain | 1031-1269 | ABC transporter 2 | ||||
Sequence: VTFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPMAGSVLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVPHDEIVRAAKEANIHPFIETLPQKYNTRVGDKGTQLSGGQKQRIAIARALIRQPRVLLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVIENGKVKEHGTHQQLLAQKGIYFSMVNI |
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
- Length1,276
- Mass (Da)140,377
- Last updated2011-06-28 v2
- Checksum30BC72EDDFA4388C
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JDM4 | A0A0G2JDM4_MOUSE | Abcb4 | 882 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 257 | in Ref. 1; AAA39516 | ||||
Sequence: L → P | ||||||
Sequence conflict | 828 | in Ref. 1; AAA39516 | ||||
Sequence: R → K |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J03398 EMBL· GenBank· DDBJ | AAA39516.1 EMBL· GenBank· DDBJ | mRNA | ||
CH466600 EMBL· GenBank· DDBJ | EDL14681.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC150687 EMBL· GenBank· DDBJ | AAI50688.1 EMBL· GenBank· DDBJ | mRNA | ||
M74151 EMBL· GenBank· DDBJ | AAA39515.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U46839 EMBL· GenBank· DDBJ | AAC52722.1 EMBL· GenBank· DDBJ | Genomic DNA |