ABCMdb

ABCC2 p.Arg1257Ala

[switch to full view]
Comments [show]

None has been submitted yet.

Publications

PMID: 12450376 [PubMed] Ren XQ et al: "A positively charged amino acid proximal to the C-terminus of TM17 of MRP1 is indispensable for GSH-dependent binding of substrates and for transport of LTC4."

No. Sentence Comment

165 The R1257A (TM17) mutant of human MRP2 showed reduced transport activity of GSH-bound meth- ylfluorescein (33). Login to comment
256 It has also been observed that R1210A (TM16) and R1257A (TM17) mutants of human MRP2 showed decreased transport activity with the GSH-methylfluorescein conjugate (33). Login to comment

PMID: 14965249 [PubMed] Haimeur A et al: "The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation."

No. Sentence Comment

400 However, four of the mutants (Lys324Ala in TM6, Lys483Ala in TM9, Arg1210Ala in TM16 and Arg1257Ala in TM17) showed decreased efflux of GSH conjugated methylfluorescein [281]. Login to comment

PMID: 20082599 [PubMed] Jemnitz K et al: "ABCC2/Abcc2: a multispecific transporter with dominant excretory functions."

No. Sentence Comment

97 Mutant Predicted location Substrate Activity changes Reference Human MRP2 Δ1-188 TMD0 LTC4 ↓ Fernandez et al., 2002 K316A JC, TM6 GMF ↔ Ryu et al., 2000 K324A TM6 GMF ↓ Ryu et al., 2000 K329A TM6 GMF ↔ Ryu et al., 2000 R412G DJ IC MTX ↓ Hulot et al., 2005 W417I IC, TM7-TM8 E2-17βG ↓ Hirouchi et al., 2004 LTC4 ↓ DNP-SG ↓ H439A TM8 GMF ↔ Ryu et al., 2000 K483A IC, JM, TM9 GMF ↓ Ryu et al., 2000 K590A JC, TM11 GMF ↔ Ryu et al., 2000 S789F NBD1 E2-17βG ↓ Hirouchi et al., 2004 LTC4 ↓ DNP-SG ↓↓ R1023A EC, JM, TM13 GMF ↔ Ryu et al., 2000 H1042A TM13 GMF ↔ Ryu et al., 2000 R1100A JC, TM14 GMF ↔ Ryu et al., 2000 P1158A IC, JM, TM15 LTC4 ↓↓ Letourneau et al., 2007 E2-17βG ↔ MTX ↔ Table 1. continued on next page Mutant Predicted location Substrate Activity changes Reference I1173F DJ IC, TM15-16 LTC4 No act Keitel et al., 2003 E2-17βG No act R1210A EC, JC, TM16 GMF ↓↓ Ryu et al., 2000 R1230A TM16 GMF ↔ R1257A JC, TM17 GMF ↓↓ W1254A JC, TM17 E2-17βG ↓↓ Ito et al., 2001a W1254C ↓↓ W1254F ↔ W1254Y ↔ W1254A JC, TM17 LTC4 ↓↓ Ito et al., 2001b W1254C ↓↓↓ W1254F ↓↓ W1254Y ↓↓ W1254A JC, TM17 MTX ↓↓ Ito et al., 2001a W1254C ↓↓ W1254F ↓↓ W1254Y ↓↓↓ A1450T NBD2 E2-17βG ↓↓ Hirouchi et al., 2004 LTC4 ↓↓ DNP-SG ↓↓ Rat Mrp2 K308M IC, JM, TM6 TLC-S ↔ Ito et al., 2001b DNP-G ↑ LTC4 ↓ E3040G ↔ K320M TM6 TLC-S ↑ DNP-G ↑ LTC4 ↓ E3040G ↑ K325M TM6 TLC-S ↓* DNP-G ↓↓↓* LTC4 ↓↓↓* E3040G ↓ D329N TM6 TLC-S ↔ DNP-G ↓ LTC4 ↓↓↓* E3040G ↓ R586L TM11 TLC-S ↓ DNP-G ↓↓* LTC4 ↓↓* E3040G ↔ R1019M IC, JM, TM13 TLC-S ↔ DNP-G ↑* LTC4 ↔ E3040G ↔ R1096L TM14 TLC-S ↑ DNP-G ↑ LTC4 ↔ E3040G ↔ EC, extracellular; IC, intracellular; JC, near the cytosol in the membrane; JM, juxtamembrane; TLC-S, tauro-litocholate-sulfate; GMF, glutathione- methyl-fluorescein; ↑, activity over control>1.2; ↔, 1.2>activity over control>0.8; ↓, 0.8>activity over control>0.5; ↓↓, 0.5>activity over control>0.1; ↓↓↓, 0.1>activity over control. Login to comment

PMID: 12406647 [PubMed] Suzuki H et al: "Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition."

No. Sentence Comment

120 It affecting MRP2 function was found that Lys24Ala (TM6), Lys483Ala (TM9), Arg210Ala (TM16) and Arg1257Ala (TM17) exhibit Several lines of investigation have been followed reduced transport activity for glutathione-conjugates to investigate the amino acid residues in MRP2 (Fig. 2) [111]. Login to comment

PMID: 12130697 [PubMed] Gerk PM et al: "Regulation of expression of the multidrug resistance-associated protein 2 (MRP2) and its role in drug disposition."

No. Sentence Comment

49 Thirteen basic residues (His, Arg, Lys) in these regions were substituted with alanine; four mutants (K324A in TM6, K483A in TM9, R1210A in TM16 and R1257A in TM17) were all delivered appropriately to the cell surface when expressed in COS-7 cells yet showed decreased efflux of the substrate (Ryu et al., 2000). Login to comment

PMID: 11477083 [PubMed] Mor-Cohen R et al: "Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome."

No. Sentence Comment

243 Interestingly, two site-directed mutations, which replaced arginine by alanine in the predicted third transmembrane region of MRP2 (R1210A and R1257A), were shown to cause FIG. 6. Login to comment

PMID: 10978330 [PubMed] Ryu S et al: "Identification of basic residues involved in drug export function of human multidrug resistance-associated protein 2."

No. Sentence Comment

3 Four mutants, K324A (TM6), K483A (TM9), R1210A (TM16), and R1257A (TM17), showed decreased transport activity, and another mutant, K578A (TM11), showed decreased protein expression. Login to comment
43 The other six mutants, R1023A, H1042A, R1100A, R1210A, R1230A, and R1257A, were generated by the method of Kunkel (30). Login to comment
120 In R1210A and R1257A mutants, the excretion of GS-MF decreased approximately to the level of control, but expression level was comparable with MRP2X (Figs. 5 and 6). Login to comment
148 Among these mutants, K578A, R1210A, and R1257A were the most influenced by mutation concerning substrate translocating activity FIG. 6. Login to comment