ABCMdb

PMID: 19285158

Fung KL, Gottesman MM
A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function.
Biochim Biophys Acta. 2009 May;1794(5):860-71. Epub 2009 Mar 11., [PubMed]

Sentences

No. Mutations Sentence Comment

145 ABCB1 p.Gly185Val A missense mutation found at position 183 is very close to two amino acids before the G185V mutation site. Login to comment 146 ABCB1 p.Gly185Val ABCB1 p.Gly185Val A missense mutation found at position 183 is very close to two amino acids before the G185V mutation site. Login to comment 147 ABCB1 p.Gly185Val This G185V mutation has been identified in drug-resistant cell lines, but not in humans. Login to comment 151 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Phe103Leu ABCB1 p.Ala999Thr A study in our lab showed that common polymorphisms of MDR1 at 61ANG (N21D), 307TNC (F103L), 1199GNA (S400N), 2677GNT (A893S) and 2995GNA (A999T) do not change the transport of four MDR1 substrates when expressed at high levels in human cells [66]. Login to comment 152 ABCC1 p.Ala893Ser ABCB1 p.Ser400Asn ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Asn21Asp ABCB1 p.Phe103Leu ABCB1 p.Ala999Thr ABCB1 p.Ser1141Thr ABCB1 p.Arg669Cys ABCB1 p.Val1251Ile A study in our lab showed that common polymorphisms of MDR1 at 61ANG (N21D), 307TNC (F103L), 1199GNA (S400N), 2677GNT (A893S) and 2995GNA (A999T) do not change the transport of four MDR1 substrates when expressed at high levels in human cells [66]. Login to comment 153 ABCC1 p.Ala893Ser ABCC1 p.Ala893Thr ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Ser1141Thr ABCB1 p.Ser1141Thr ABCB1 p.Arg669Cys ABCB1 p.Arg669Cys ABCB1 p.Leu662Arg ABCB1 p.Val1251Ile ABCB1 p.Met89Thr ABCB1 p.Trp1108Arg A recent study by Gow et al. suggested that all of the SNPs they tested (N21D, S400N, R669C, A893S, A893T, S1141T, V1251I) produced small changes which in most cases are not statistically significant [59]. Login to comment 154 ABCC1 p.Ala893Ser ABCB1 p.Ser1141Thr ABCB1 p.Arg669Cys ABCB1 p.Leu662Arg ABCB1 p.Met89Thr ABCB1 p.Trp1108Arg Another study using a yeast host to express human MDR1 SNPs (M89T, L662R, R669C, A893S, W1108R, S1141T) showed increased resistance to anthracyclines, actinomycin D and valinomycin. Login to comment 185 ABCC1 p.Ala893Ser ABCC1 p.Ala893Thr The occurrence of 2677GNT (A893S) is far more frequent than G2677A (A893T). Login to comment 226 ABCB1 p.Asn21Asp Protein function is different depending on substrate use 1236T-3435T 2677T-3435T 1236T-2677T-3435T 1236T-2677T-3435A Hung CC et al. 2008 [93] Flp-In HEK-293 Stable No difference 1236T-2677A Rhodamine 123 Calcein-AM, phenytoin, cyclosporine A, phenobarbital valproic acid, lamotrigine, carbamazepine, gabapentin, levetiracetam Certain inhibitors against Rhodamine 123 transport are less effective in double haplotype and TTT haplotype 1236T-2677T 1236T-3435T 2677A-3435T 2677T-3435T 1236T-2677A-3435T 1236T-2677T-3435T Salama NN et al. 2006 [91] LLC-PK1 Stable No apparent difference 1236T-2677T Rhodamine 123, vincristine, vinblastine Single or haplotype mutations had significant decrease in MDR1 function 1236T-3435T 2677T-3435T 1236T-2677T-3435T GOW JM et al. 2008 [59] HEK-293T Transient No difference 1236T-2677T-3435T Calcein-AM, cyclosporine A, BODIPY-FL-paclitaxel TTT haplotype with N21D mutation reduces MDR1 function with BODIPY-FL-paclitaxel but not Calcein-AM. Login to comment 227 ABCB1 p.Asn21Asp Protein function is different depending on substrate use 1236T-3435T 2677T-3435T 1236T-2677T-3435T 1236T-2677T-3435A Hung CC et al. 2008 [93] Flp-In HEK-293 Stable No difference 1236T-2677A Rhodamine 123 Calcein-AM, phenytoin, cyclosporine A, phenobarbital valproic acid, lamotrigine, carbamazepine, gabapentin, levetiracetam Certain inhibitors against Rhodamine 123 transport are less effective in double haplotype and TTT haplotype 1236T-2677T 1236T-3435T 2677A-3435T 2677T-3435T 1236T-2677A-3435T 1236T-2677T-3435T Salama NN et al. 2006 [91] LLC-PK1 Stable No apparent difference 1236T-2677T Rhodamine 123, vincristine, vinblastine Single or haplotype mutations had significant decrease in MDR1 function1236T-3435T 2677T-3435T 1236T-2677T-3435T GOW JM et al. 2008 [59] HEK-293T Transient No difference 1236T-2677T-3435T Calcein-AM, cyclosporine A, BODIPY-FL-paclitaxel TTT haplotype with N21D mutation reduces MDR1 function with BODIPY-FL-paclitaxel but not Calcein-AM. Login to comment 341 ABCB1 p.Ser400Asn Several amino acid residues around this SNP (e.g., Y401, S400N) are essential for ATP-binding and ATP hydrolysis [42,49]. Login to comment 342 ABCB1 p.Ser400Asn Several amino acid residues around this SNP (e.g., Y401, S400N) are essential for ATP-binding and ATP hydrolysis [42,49]. Login to comment 351 ABCB1 p.Gly830Val ABCB1 p.Ile849Met Nevertheless, mutation studies have identified several amino acids (G830V, I849M) that could change the kinetics of drug-induced ATPase activity [42,116]. Login to comment 352 ABCB1 p.Gly830Val ABCB1 p.Ile849Met Nevertheless, mutation studies have identified several amino acids (G830V, I849M) that could change the kinetics of drug-induced ATPase activity [42,116]. Login to comment