TY - JOUR
T1 - Predicted mouse peroxisome-targeted proteins and their actual subcellular locations
AU - Mizuno, Yumi
AU - Kurochkin, Igor V.
AU - Herberth, Marlis
AU - Okazaki, Yasushi
AU - Schönbach, Christian
PY - 2008/12/12
Y1 - 2008/12/12
N2 - Background: The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences. Results: We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARα mediated activation. Notably, none of the PTS2 candidates located to peroxisomes. Conclusion: In a few cases the PTS may oscillate from "silent" to "functional" depending on its surface accessibility indicating the potential for context-dependent conditional subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve without generation and integration of new experimental data from location proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays.
AB - Background: The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences. Results: We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARα mediated activation. Notably, none of the PTS2 candidates located to peroxisomes. Conclusion: In a few cases the PTS may oscillate from "silent" to "functional" depending on its surface accessibility indicating the potential for context-dependent conditional subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve without generation and integration of new experimental data from location proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays.
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U2 - 10.1186/1471-2105-9-S12-S16
DO - 10.1186/1471-2105-9-S12-S16
M3 - Article
C2 - 19091015
AN - SCOPUS:57649201317
VL - 9
SP - S16
JO - BMC Bioinformatics
JF - BMC Bioinformatics
SN - 1471-2105
IS - SUPPL. 12
ER -