Not all GPCRs are predicted to have signal peptides (e.g. many mammalian Family A GPCRs) but it is important to check, especially if N-terminal peptide-tagging experiments are to be performed. There are several reported methods in the literature and on the web, but SignalP is the probably the most used publicly available program (Nielsen etal. 1999), accessible over the internet at the Center for Biological Sequence Analysis (http://www.cds.dtu.dk/services).
Excellent instructions for using the program are given on the web site, and it is important to use only the N-terminal part of the sequence. This will avoid predictions of abnormally long signal peptides that are likely to be false predictions within transmembrane domains.
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