ABCC4 p.Ile1103Val
| Predicted by SNAP2: | A: N (78%), C: N (87%), D: D (66%), E: D (53%), F: N (87%), G: N (61%), H: N (87%), K: D (53%), L: N (97%), M: N (97%), N: N (78%), P: D (71%), Q: N (72%), R: N (87%), S: N (78%), T: N (93%), V: N (97%), W: D (59%), Y: N (93%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: N, |
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[hide] Role of glutathione in the multidrug resistance pr... Biochem J. 2002 Feb 1;361(Pt 3):497-503. Lai L, Tan TM
Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues.
Biochem J. 2002 Feb 1;361(Pt 3):497-503., [PMID:11802779]
Abstract [show]
Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.
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No. Sentence Comment
81 The translated protein sequence was identical with the published sequence (GenBank accession number AF071202), except for changes at position 18 (Ile to Leu), position 637 (Glu to Gly), position 664 (Ser to Phe), position 1103 (Ile to Val), position 1139 (Lys to Asn) and position 1289 (Lys to Arg).
X
ABCC4 p.Ile1103Val 11802779:81:222
status: NEW