ABCC2 p.Ser283Asp
| Predicted by SNAP2: | A: N (87%), C: N (82%), D: N (93%), E: N (93%), F: N (78%), G: N (87%), H: N (87%), I: N (78%), K: N (93%), L: N (78%), M: N (87%), N: N (93%), P: N (82%), Q: N (93%), R: N (87%), T: N (93%), V: N (87%), 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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[hide] A cis-acting five-amino-acid motif controls target... J Cell Sci. 2012 Jul 1;125(Pt 13):3133-43. Epub 2012 Mar 27. Emi Y, Yasuda Y, Sakaguchi M
A cis-acting five-amino-acid motif controls targeting of ABCC2 to the apical plasma membrane domain.
J Cell Sci. 2012 Jul 1;125(Pt 13):3133-43. Epub 2012 Mar 27., [PMID:22454528]
Abstract [show]
ATP-binding cassette transporter isoform C2 (ABCC2) is exclusively targeted to the apical plasma membrane of polarized cells. Although apical localization of ABCC2 in hepatocytes is crucial for the biliary excretion of a variety of metabolites, the mechanism regulating its apical targeting is poorly understood. In the present study, an apical targeting signal was identified in the first cytoplasmic loop domain (CLD1) of ABCC2 in HepG2 cells. Overexpression of CLD1 significantly disturbed the apical targeting of FLAG-ABCC2 in a competitive manner, suggesting the presence of a saturable sorting machinery in HepG2 cells. Next, deletion analysis identified a potential targeting sequence within a 20-amino-acid long peptide (aa 272-291) of CLD1. Alanine scanning mutagenesis of this region in full-length ABCC2 further narrowed down the apical targeting determinant to five amino acids, S(283)QDAL(287). Of these, S(283) and L(287) were found to be conserved among vertebrate ABCC2 orthologs. Site-directed mutagenesis showed that both S(283) and L(287) were crucial for the targeting specificity of ABCC2. Introducing this apical targeting sequence into the corresponding region of ABCC1, an exclusively basolateral protein, caused the hybrid ABCC1 to partially localize in the apical membrane. Thus, the CLD1 of ABCC2 contains a novel apical sorting determinant, and a saturable sorting machinery is present in polarized HepG2 cells.
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No. Sentence Comment
141 Notably, two mutants containing phosphomimetic substitutions at residue S283 , namely S283D and S283E, exhibited normal apical localization similar to that of the wild-type ABCC2 (Fig. 5).
X
ABCC2 p.Ser283Asp 22454528:141:86
status: NEW159 The S283A mutant lost its apical-specific steering activity and gave the mixed staining of the lateral side in addition to the apical side, whereas the S283D phosphomimetic substitution restored apical-specific localization.
X
ABCC2 p.Ser283Asp 22454528:159:152
status: NEW266 ABCC2 mutants containing phosphomimetic substitutions at S283 (S283D and S283E) showed normal apical localization, whereas mutants containing nonphosphorylatable substitutions at S283 were localized to both the apical and basolateral membranes.
X
ABCC2 p.Ser283Asp 22454528:266:63
status: NEW139 Notably, two mutants containing phosphomimetic substitutions at residue S283 , namely S283D and S283E, exhibited normal apical localization similar to that of the wild-type ABCC2 (Fig. 5).
X
ABCC2 p.Ser283Asp 22454528:139:86
status: NEW156 The S283A mutant lost its apical-specific steering activity and gave the mixed staining of the lateral side in addition to the apical side, whereas the S283D phosphomimetic substitution restored apical-specific localization.
X
ABCC2 p.Ser283Asp 22454528:156:152
status: NEW263 ABCC2 mutants containing phosphomimetic substitutions at S283 (S283D and S283E) showed normal apical localization, whereas mutants containing nonphosphorylatable substitutions at S283 were localized to both the apical and basolateral membranes.
X
ABCC2 p.Ser283Asp 22454528:263:63
status: NEW262 ABCC2 mutants containing phosphomimetic substitutions at S283 (S283D and S283E) showed normal apical localization, whereas mutants containing nonphosphorylatable substitutions at S283 were localized to both the apical and basolateral membranes.
X
ABCC2 p.Ser283Asp 22454528:262:63
status: NEW