ABCMdb

PMID: 10331089

Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM
Biochemical, cellular, and pharmacological aspects of the multidrug transporter.
Annu Rev Pharmacol Toxicol. 1999;39:361-98., [PubMed]

Sentences

No. Mutations Sentence Comment

47 ABCB1 p.Gly324Lys ABCB1 p.Gln990Ala ABCB1 p.Gly288Val ABCB1 p.Pro866Ala ABCB1 p.Val981Ala ABCB1 p.Val981Ala ABCB1 p.Val981Ala ABCB1 p.Val988Ala ABCB1 p.Ile299Met ABCB1 p.His61Arg ABCB1 p.Gly185Val ABCB1 p.Gly185Val ABCB1 p.Gly64Arg ABCB1 p.Phe978Ala ABCB1 p.Gly187Val ABCB1 p.Ser351Asn ABCB1 p.Thr941Ala ABCB1 p.Leu65Arg ABCB1 p.Phe938Ala ABCB1 p.Met986Ala ABCB1 p.Phe204Ser ABCB1 p.Lys536Arg ABCB1 p.Asn183Ser ABCB1 p.Val338Ala ABCB1 p.Val991Ala ABCB1 p.Pro223Ala ABCB1 p.Phe335Ala ABCB1 p.Phe983Ala ABCB1 p.Phe983Ala ABCB1 p.Phe983Ala ABCB1 p.Phe983Ala ABCB1 p.Leu975Ala ABCB1 p.Leu975Ala ABCB1 p.Leu975Ala ABCB1 p.Gly341Val ABCB1 p.Thr319Ser ABCB1 p.Leu322Ile ABCB1 p.Gly830Val ABCB4 p.Gln145His ABCB4 p.Tyr949Ala ABCB4 p.Ile936Ala Table 1 List of mutations in human, mouse, and hamster P-glycoproteins that affect substrate specificitya aa mutation Region Sourceb Reference H61R, F, K, M, W, Y TM 1 Human MDR1 149, 150 ABC20c G64R TM 1 Human MDR1 150 L65R TM 1 Human MDR1 150 aa78-97 EC 1 Human MDR1 151 Q128Hd TM 2 Mouse mdr3 152 R138H IC 1 Mouse mdr3 152 Q139H, R IC 1 Mouse mdr3 152 Q141V IC 1 Human MDR1 15319, Q145H IC 1 Mouse mdr3 152 E155G, K IC 1 Mouse mdr3 152 F159I IC 1 Mouse mdr3 152 D174G IC 1 Mouse mdr3 152 S176G, P IC 1 Mouse mdr3 152 K177I IC 1 Mouse mdr3 152 N179S IC 1 Mouse mdr3 152 N183S/G185V IC 1 Human MDR1 154 G183D IC 1 Mouse mdr3 152 G185V IC 1 Human MDR1 155-157 G187V IC 1 Human MDR1 153 A192T TM 3 Mouse mdr3 152 F204S EC 2 Mouse mdr3 152 W208G EC 2 Mouse mdr3 152 K209E EC 2 Mouse mdr3 152 L210I TM 4 Mouse mdr3 152 T211P TM 4 Mouse mdr3 152 I214T TM 4 Mouse mdr3 152 P223A TM 4 Human MDR1 158 G288V IC 2 Human MDR1 153 I299M, T319S, L322I, TM 5, EC3, Human MDR1 159 G324K, S351N IC 3 F335A TM 6 Human MDR1 19 F335 TM 6 Human MDR1 160 V338A TM 6 Human MDR1 161 G338A, A339P TM 6 Hamster PGY1 162, 163 A339P TM 6 Hamster PGY1 163 G341V TM 6 Human MDR1 161 K536R, Q N-NBD Human MDR1 164 ERGA → DKGT N-NBD Mouse mdr3 165 aa 522-525 T578C N-NBD Mouse mdr3 165 (Continued) G830V IC 4 Human MDR1 P866A TM 10 Human MDR1 158 F934A TM 11 Mouse mdr3 166 G935A TM 11 Mouse mdr3 166 I936A TM 11 Mouse mdr3 166 F938A TM 11 Mouse mdr3 166 S939A TM 11 Mouse mdr3 166 S939F TM 11 Mouse mdr3 167, 168 S941F TM 11 Mouse mdr1 167, 168 T941A TM 11 Mouse mdr3 166 Q942A TM 11 Mouse mdr3 166 A943G TM 11 Mouse mdr3 166 Y946A TM 11 Mouse mdr3 166 S948A TM 11 Mouse mdr3 166 Y949A TM 11 Mouse mdr3 166 C952A TM 11 Mouse mdr3 166 F953A TM 11 Mouse mdr3 166 F983A TM 12 Human MDR1 169 L975A, V981A, F983A TM 12 Human MDR1 169 M986A, V988A, Q990A, TM 12 Human MDR1 169 V991A V981A, F983A TM 12 Human MDR1 169 L975A, F983A TM 12 Human MDR1 169 L975A, V981A TM 12 Human MDR1 169 F978A TM 12 Human MDR1 19 a aa,amino acid; EC, extracellular loop; IC, intracellular loop; TM,transmembrane domain; NBD, nucleotide binding/utilization domain. Login to comment 52 ABCB1 p.Gly812Val Table 1 aa mutation Region Sourceb Reference (Continued) G812V IC 4 Human MDR1 153 15319, Taken together, these mutational data suggest that the two halves of human P-gp interact to form a single transporter and that the major drug binding domains reside in or near transmembrane domains 5, 6 and 11, 12. Login to comment 490 ABCB1 p.Gly185Val 1996. Functional characterization of a glycine 185-to-valine substitution in human P-glycoprotein by using a vaccinia-based transient expression system. Mol. Login to comment