P-glycoprotein 3 (PGY3, multidrug resistance protein 3, MDR3, ATP-binding cassette subfamily B member 4, ABC4)

Mediates the translocation of phosphatidylcholine across the canalicular membrane of hepatocytes. Function: - energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells - mediates translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte - human MDR3 is not capable of conferring drug resistance Structure: - belongs to the ABC transporter family, multidrug resistance exporter (TC 3.A.1.201) subfamily - contains 2 ABC transmembrane type-1 domains - contains 2 ABC transporter domains Compartment: membrane Alternative splicing: named isoforms=2 Pathology: - defects in ABCB4 are the cause of a) familial intrahepatic cholestasis 3 b) intrahepatic cholestasis of pregnancy c) cholelithiasis - genetic variations in ABCB4 may play a role in drug- induced cholestasis causing liver damage

General

ATP-binding cassette sub-family B (ABC transporter-B, ABCB) phosphoprotein P-glycoprotein (gp170) or multidrug-resistance glycoprotein

Properties

SIZE: entity length = 1279 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-57} transmembrane domain {58-78} exoplasmic loop {79-122} MOTIF: N-glycosylation site {N91} N-glycosylation site {N97} transmembrane domain {123-143} cytoplasmic loop {144-191} transmembrane domain {192-211} exoplasmic loop {212-215} transmembrane domain {216-235} cytoplasmic loop {236-300} transmembrane domain {301-320} exoplasmic loop {321-335} transmembrane domain {336-354} cytoplasmic loop {355-711} MOTIF: ATP-binding site NAME: ATP-binding site SITE: 429-436 transmembrane domain {712-732} exoplasmic loop {733-755} transmembrane domain {756-776} cytoplasmic loop {777-831} transmembrane domain {832-851} exoplasmic loop {852-853} transmembrane domain {854-873} cytoplasmic loop {874-936} transmembrane domain {937-956} exoplasmic loop {957-975} transmembrane domain {976-993} cytoplasmic domain {994-1279} MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1069-1076 SUBSTRATE: colchicine CYLOSPORIN digoxin diltiazem etoposide glucocorticoid* nicardipine paclitaxel verapamil vinblastine vincristine VINDESINE INDUCERS: Hypericum perforatum INHIBITORS: amiodarone clarithromycin cyclosporin A diltiazem erythromycin indinavir itraconazole ketoconazole nicardipine ritonavir verapamil

Database Correlations

OMIM correlations MORBIDMAP 171060 UniProt P21439 PFAM correlations Entrez Gene 5244