P-glycoprotein 1 (PGY1, multidrug resistance protein 1, MDR1, gp170, ATP-binding cassette subfamily B member 1, ABCB1)

Function: - energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells - P-glycoprotein 1 helps eliminate drugs by pumping them OUT of cells, back into the gut, bile, & urine for excretion - substrates - colchicine - cyclosporin - digoxin - diltiazem - etoposide - glucocorticoids - mefloquine - nicardipine - paclitaxel - verapamil - vinblastine - vincristine - vindesine 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 Expression: - expressed in liver, kidney, small intestine & brain - inducers: St John's wort - inhibitors: - amiodarone - clarithromycin - cyclosporin - diltiazem - erythromycin - indinavir - itraconazole - ketoconazole - nicardipine - ritonavir - verapamil Polymorphism: - genetic variation in ABCB1 may play a role in patients who do not respond to drug treatment - polymorphisms in ABCB1 may predispose to neuropsychiatric adverse effects of mefloquine [3] Pathology: - tumor cells may up-relate P-glycoprotein 1 as a mechanism for development of resistance to antineoplastic agents

General

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

Properties

SIZE: MW = 141 kD entity length = 1280 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-51} transmembrane domain {52-72} exoplasmic loop {73-119} N-glycosylation site {N91} N-glycosylation site {N94} N-glycosylation site {N99} transmembrane domain {120-140} cytoplasmic loop {141-188} transmembrane domain {189-209} exoplasmic loop {210-215} transmembrane domain {216-236} cytoplasmic loop {237-296} transmembrane domain {297-317} exoplasmic loop {318-325} transmembrane domain {326-346} cytoplasmic loop {347-710} MOTIF: ABC TRANSPORTER 1 {392-628} ATP-binding site NAME: ATP-binding site SITE: 427-434 transmembrane domain {711-731} exoplasmic loop {732-756} transmembrane domain {757-777} cytoplasmic loop {778-832} transmembrane domain {833-853} exoplasmic loop {854-853} transmembrane domain {854-874} cytoplasmic loop {875-936} transmembrane domain {937-957} exoplasmic loop {958-973} transmembrane domain {974-994} cytoplasmic domain {995-1280} MOTIF: ABC TRANSPORTER 2 {1035-1273} ATP-binding site NAME: ATP-binding site SITE: 1070-1077 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 171050 UniProt P08183 Entrez Gene 5243