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Details on Person UniProt:P21439-1 ABCB4
| Class:Id | ReferenceIsoform:403286 |
|---|---|
| _chainChangeLog | chain:1-1286 added on Fri February 6 2015 |
| _displayName | UniProt:P21439-1 ABCB4 |
| _timestamp | 2025-02-21 19:49:59 |
| chain | chain:1-1286 |
| checksum | 9A9066F2292F2CCF |
| comment | 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 of 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:17523162, PubMed:21820390, PubMed:23468132, PubMed:24594635, PubMed:24723470, PubMed:24806754, PubMed:31873305, PubMed:7957936, PubMed:8898203, 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 (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:28012258, 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 (By similarity).CATALYTIC ACTIVITY ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + phosphate + H(+)CATALYTIC ACTIVITY a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+)ACTIVITY REGULATION Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:17523162, PubMed:23468132). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:17523162, PubMed:23468132).BIOPHYSICOCHEMICAL PROPERTIES May interact with RACK1 (PubMed:19674157). Interacts with HAX1 (By similarity).SUBCELLULAR LOCATION Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (By similarity). Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner (PubMed:19674157). Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner (PubMed:15258199). Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132).ALTERNATIVE PRODUCTS Up-regulated by PPARA (PubMed:24122873). Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate (at protein level). Up-regulated by bezafibrate (PubMed:15258199). Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, bezafibrate and gemfibrozil (PubMed:24122873).PTM Phosphorylated (PubMed:24723470). Phosphorylation on Thr-34 is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner (PubMed:24723470). May be phosphorylated on Thr-44 and Ser-49 (PubMed:24723470).PTM Glycosylated (PubMed:17523162, PubMed:21820390, PubMed:24723470).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.SEQUENCE CAUTION Probable cloning artifact.ONLINE INFORMATION Database for mutations in ABC proteins |
| created | [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 |
| description | recommendedName: fullName evidence="41"Phosphatidylcholine translocator ABCB4 ecNumber evidence="2"7.6.2.1 alternativeName: fullName evidence="43"ATP-binding cassette sub-family B member 4 alternativeName: fullName evidence="39"Multidrug resistance protein 3 alternativeName: fullName evidence="3"P-glycoprotein 3 |
| geneName | ABCB4 MDR3 PGY3 |
| identifier | P21439 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Cytoplasm Cytoplasmic vesicle Disease variant Glycoprotein Intrahepatic cholestasis Lipid transport Membrane Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Repeat Translocase Transmembrane Transmembrane helix Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | ABCB4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:5649917] ENSEMBL:ENSG00000005471 ABCB4 [Homo sapiens] |
| secondaryIdentifier | MDR3_HUMAN A0A2V7 A4D1D3 A4D1D4 A4D1D5 D6W5P3 D6W5P4 Q14813 |
| sequenceLength | 1286 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P21439-1 |
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No pathways have been reviewed or authored by UniProt:P21439-1 ABCB4 (403286)
