ABCC2 p.Ile448Val
| Predicted by SNAP2: | A: D (59%), C: N (53%), D: D (85%), E: D (80%), F: D (59%), G: D (75%), H: D (80%), K: D (85%), L: N (53%), M: N (61%), N: D (80%), P: D (85%), Q: D (75%), R: D (85%), S: D (66%), T: D (66%), V: N (82%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Identification of basic residues involved in drug ... J Biol Chem. 2000 Dec 15;275(50):39617-24. Ryu S, Kawabe T, Nada S, Yamaguchi A
Identification of basic residues involved in drug export function of human multidrug resistance-associated protein 2.
J Biol Chem. 2000 Dec 15;275(50):39617-24., [PMID:10978330]
Abstract [show]
Multidrurg resistance-associated protein 2 (MRP2)/canalicular multispecific organic anion transporter (cMOAT) is involved in the ATP-dependent export of organic anions across the bile canalicular membrane. To identify functional amino acid residues that play essential roles in the substrate transport, each of 13 basic residues around transmembrane regions (TMs) 6-17 were replaced with alanine. Wild type and mutant proteins were expressed in COS-7 cells, and the transport activity was measured as the excretion of glutathione-methylfluorescein. Four mutants, K324A (TM6), K483A (TM9), R1210A (TM16), and R1257A (TM17), showed decreased transport activity, and another mutant, K578A (TM11), showed decreased protein expression. These five mutants were normally delivered to the cell surface similar to the other fully active mutants and wild type MRP2. The importance of TM6, TM16, and TM17 in the transport function of MRP2 is consistent with the previous observation indicating the importance of the corresponding TM1, TM11, and TM12 on P-glycoprotein (Loo, T. W., and Clarke, D. M. (1999) J. Biol. Chem. 274, 35388-35392). Another observation that MRP2 inhibitor, cyclosporine A, failed to inhibit R1230A specifically, indicated the existence of its binding site within TM16.
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No. Sentence Comment
41 For mutagenesis, we constructed pCI-neo/ MRP2X, which contains a deletion of XhoI site in the multicloning site of pCI-neo, and pCI-neo/MRP2V, which contains I448V and L653V mutations by overlapping polymerase chain reaction mutagenesis method to create Sse8387I and MluI sites, respectively.
X
ABCC2 p.Ile448Val 10978330:41:158
status: NEW113 GS-MF Excretion of Mutant MRP2 Proteins-First of all, we examined the excretion of GS-MF from COS-7 cells transfected with pCI-neo/MRP2V, which contains conservative amino acid changes as I448V and L653V, or pCI-neo/MRP2X, which contains a small deletion at the multi-cloning site of the vector.
X
ABCC2 p.Ile448Val 10978330:113:188
status: NEW144 pCI-neo/MRP2V contains mutations of I448V and L653V, which were located in TM8 and NBD1, respectively. In patients with Dubin-Johnson syndrome, loss of function mutations was occasionally found in NBD1 (12).
X
ABCC2 p.Ile448Val 10978330:144:36
status: NEW