ABCMdb

ABCC2 p.Ser1542Ala

Predicted by SNAP2:	A: N (87%), C: N (66%), D: N (82%), E: N (87%), F: N (66%), G: N (82%), H: N (93%), I: N (78%), K: N (87%), L: N (72%), M: N (72%), N: N (93%), P: N (66%), Q: N (82%), R: N (82%), T: N (93%), V: N (78%), W: D (53%), Y: N (66%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: N, Y: N,

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Publications
[hide] C-terminal phosphorylation of MRP2 modulates its i... Biochem Biophys Res Commun. 2003 Mar 14;302(3):454-61. Hegedus T, Sessler T, Scott R, Thelin W, Bakos E, Varadi A, Szabo K, Homolya L, Milgram SL, Sarkadi B
C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins.
Biochem Biophys Res Commun. 2003 Mar 14;302(3):454-61., [PMID:12615054]

Abstract [show]
MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in the targeting of MRP2, we found a potential PKC phosphorylation site (Ser(1542)). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, beta2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas beta2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2.

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Sentences [show]
No. Sentence Comment
38 The binding of EBP50 and IKEPP was studied to mutant MRP2 variants (S1542A and S1542E), mimicking the non-phosphorylated and the phosphorylated serine, respectively. Login to comment
104 In order to investigate the role of this residue in PDZ interactions, the serine was replaced either by alanine (MRP2 S1542A) or by glutamic acid (MRP2 S1542E). Login to comment
105 MRP2 S1542A mimicked the dephosphorylated, while MRP2 S1542E the phosphorylated states of the PDZ binding motif. Login to comment
107 The MRP2 S1542E mutant interacted with EBP50 much stronger than the wild type MRP2, whereas the MRP2 S1542A variant showed less EBP50 binding compared to the wild type MRP2. Login to comment
109 The autoradiogram shown in Fig. 3B reveals that the MRP2 S1542E mutant bound IKEPP much more efficiently than the wild type MRP2. Login to comment
119 However, the binding of IKEPP to the MRP2 S1542A mutant was found to be similar to the interaction with the wild type. Login to comment
121 Similar experiments with EBP50 showed a preferential binding of this PDZ protein to MRP2 S1542E at various EBP50 concentrations (data not shown). Login to comment
141 Wild type (WT), mutants mimicking the phosphorylated (S1542E) and dephosphorylated (S1542A) states of PDZ binding motif, and a variant containing glycines in place of the last four, C-terminal amino acids (4G), were studied. Login to comment
39 The binding of EBP50 and IKEPP was studied to mutant MRP2 variants (S1542A and S1542E), mimicking the non-phosphorylated and the phosphorylated serine, respectively. Login to comment
106 In order to investigate the role of this residue in PDZ interactions, the serine was replaced either by alanine (MRP2 S1542A) or by glutamic acid (MRP2 S1542E). Login to comment
143 Wild type (WT), mutants mimicking the phosphorylated (S1542E) and dephosphorylated (S1542A) states of PDZ binding motif, and a variant containing glycines in place of the last four, C-terminal amino acids (4G), were studied. Login to comment

[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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Sentences [show]
No. Sentence Comment
115 E, S1542A, mutation of the serine produced a less distinct distribution. Login to comment