ValidNESs: a database of validated leucine-rich nuclear export signals

Abstract

ValidNESs (http://validness.ym.edu.tw/) is a new database for experimentally validated leucine-rich nuclear export signal (NES)-containing proteins. The therapeutic potential of the chromosomal region maintenance 1 (CRM1)-mediated nuclear export pathway and disease relevance of its cargo proteins has gained recognition in recent years. Unfortunately, only about one-third of known CRM1 cargo proteins are accessible in a single database since the last compilation in 2003. CRM1 cargo proteins are often recognized by a classical NES (leucine-rich NES), but this signal is notoriously difficult to predict from sequence alone. Fortunately, a recently developed prediction method, NESsential, is able to identify good candidates in some cases, enabling valuable hints to be gained by in silico prediction, but until now it has not been available through a web interface. We present ValidNESs, an integrated, up-to-date database holding 221 NES-containing proteins, combined with a web interface to prediction by NESsential.

Figure 1.

Pie chart of species. Distribution of entries in ValidNESs. The number of species in which NES-containing proteins were validated are indicated in parenthesis.

Figure 2.

Sequence logos for NES sites. Sequence logos generated by the WebLogo server for NES motif matches after removing redundant sequences (with sequence identity >25%) and aligning the three hydrophobic positions within the motif. In general, the preference for negatively charged residues is lower than previously observed in NESbase. (A) Sequence logo for 6-mer NES motif matches with upstream and downstream 10-mer flanks (227 sites). (B) Sequence logo for 7-mer NES motif matches with upstream and downstream 10-mer flanks (162 sites).

Figure 3.

An overview of the search and search result interfaces in ValidNESs. ValidNESs stores metadata in two tables and provides three search functions to access these data. Once users submit their queries, the search result in text file format and FASTA format (for table of NES-containing proteins only) is generated for download. Meanwhile, ValidNESs also displays an online table for quick browsing.