ABCC2 p.Lys1544Ala
| Predicted by SNAP2: | A: N (61%), C: D (53%), D: D (53%), E: N (82%), F: D (66%), G: D (53%), H: N (66%), I: N (61%), L: N (66%), M: N (66%), N: N (61%), P: D (59%), Q: N (87%), R: N (82%), S: N (82%), T: N (78%), V: N (61%), W: D (71%), Y: D (63%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Identification of the apical membrane-targeting si... J Biol Chem. 2001 Jun 15;276(24):20876-81. Epub 2001 Mar 27. Harris MJ, Kuwano M, Webb M, Board PG
Identification of the apical membrane-targeting signal of the multidrug resistance-associated protein 2 (MRP2/MOAT).
J Biol Chem. 2001 Jun 15;276(24):20876-81. Epub 2001 Mar 27., [PMID:11274200]
Abstract [show]
The human canalicular multispecific organic anion transporter (cMOAT), known as the multidrug resistance-associated protein 2 (MRP2), is normally expressed in the liver and to a lesser extent in the kidney proximal tubules. In these tissues MRP2 specifically localizes to the apical membrane. The construction of MRP2 fused to the green fluorescent protein, and subsequent site-directed mutagenesis enabled the identification of a targeting signal in MRP2 that is responsible for its apical localization in polarized cells. The specific apical localization of MRP2 is due to a C-terminal tail that is not present in the basolaterally targeted MRP1. Deletion of three amino acids from the C-terminal of MRP2 (DeltaMRP2) causes the protein to be localized predominantly in the basolateral membrane in polarized Madin-Darby canine kidney cells. Interestingly, MRP2 expressed in a mouse leukemia cell line (L1210 cells) predominantly accumulates intracellularly with minimal cell membrane localization. In contrast, DeltaMRP2 was shown to predominantly localize in the cell membrane in L1210 cells. Increased transport of 2,4-dinitrophenyl glutathione from L1210 cells expressing DeltaMRP2 showed that the re-targeted protein retains its normal function.
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No. Sentence Comment
97 The T1543A and K1544A mutants had both apical and basolateral targeting (nonpolarized distribution) with an increase in protein accumulation in intracellular vesicles.
X
ABCC2 p.Lys1544Ala 11274200:97:15
status: NEW112 B, the K1544A mutation also lost polarized distribution of the protein with the protein detected in the apical and basolateral membranes.
X
ABCC2 p.Lys1544Ala 11274200:112:7
status: NEW166 The canonical PDZ domain is reported to tolerate any residue (X) at the -1 position, but the K1544A caused nonpolarized targeting, suggesting some flexibility in the constraints determining functional PDZ domains.
X
ABCC2 p.Lys1544Ala 11274200:166:93
status: NEW