Nucleotide sugar transporters (NST) establish the functional link of membrane transport between the nucleotide sugars synthesized in the cytoplasm and nucleus, and the glycosylation processes that take place in the endoplasmic reticulum (ER) and Golgi apparatus. The aim of the present work was to perform a phylogenetic analysis of 87 bank annotated protein sequences comprising all the NST so far characterized and their homologues retrieved by BLAST searches, as well as the closely related triose-phosphate translocator (TPT) plant family. NST were classified in three comprehensive families by linking them to the available experimental data. This enabled us to point out both the possible ER subcellular targeting of these transporters mediated by the dy-lysine motif and the substrate recognition mechanisms specific to each family as well as an important acceptor site motif, establishing the role of evolution in the functional properties of each NST family.
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