Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Details on Person UniProt:P21439 ABCB4

Class:Id	ReferenceGeneProduct:59119
_chainChangeLog	chain:1-1286 added on Fri February 6 2015
_displayName	UniProt:P21439 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
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
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
(isoformParent)	[ReferenceIsoform:236948] UniProt:P21439-2 ABCB4 [Homo sapiens] [ReferenceIsoform:403286] UniProt:P21439-1 ABCB4 [Homo sapiens] [ReferenceIsoform:8971533] UniProt:P21439-3 ABCB4 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:400167] ABCB4 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678748] ABCB4 R957* [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678777] ABCB4 P1161S [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678814] ABCB4 V571Dfs16 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678826] ABCB4 Y403H [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678839] ABCB4 R144 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678865] ABCB4 T175V [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678907] ABCB4 R590Q [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678946] ABCB4 R545G [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5678948] ABCB4 A546D [plasma membrane] [Homo sapiens]
(referenceSequence)	[ReplacedResidue:5678780] L-arginine 590 replaced with L-glutamine [ReplacedResidue:5678783] L-tyrosine 403 replaced with L-histidine [NonsenseMutation:5678785] Nonsense mutation at L-arginine 957 [ReplacedResidue:5678833] L-threonine 175 replaced with L-valine [ReplacedResidue:5678838] L-arginine 545 replaced with glycine [FragmentReplacedModification:5678872] Replacement of residues 571 to 585 by DRQLWIRPEKAGPPL [ReplacedResidue:5678888] L-alanine 546 replaced with L-aspartic acid [NonsenseMutation:5678902] Nonsense mutation at L-arginine 144 [ReplacedResidue:5678918] L-proline 1161 replaced with L-serine
[Change default viewing format]

No pathways have been reviewed or authored by UniProt:P21439 ABCB4 (59119)