TRG_NES_CRM1_1

The import-export protein traffic through the nuclear envelope is mediated by soluble transport receptors (carriers) termed importins and exportins that bind to specific signals present within their substrates. The best-characterized export carrier is CRM1 (also known as exportin1/Xpo1), an evolutionarily well-conserved protein. The CRM1-mediated export is inhibited by the fungicide leptomycin B (LMB), providing a unique experimental tool for studying nuclear localization and trafficking in eukaryotic cells. The NES signal was first identified in the HIV Rev protein and in the Protein Kinase A inhibitor (PKI-alpha). The majority of the export substrates of CRM1 contain a Leucine-rich Nuclear Export signal (NES) consisting of 4-5 hydrophobic residues in a region of ~ 10 amino acids. The NetNES 1.1 server predicts leucine-rich nuclear export signals (NES) in eukaryotic proteins using a combination of neural networks and hidden Markov models.
Genuine NES motifs appear to be always in regions of natively disordered peptide. Clashes with known globular domains should be assumed to indicate non-viability of the motif candidate. However, NES motifs can be found close in sequence to known domains and may conditionally bind to them in a closed conformation. Regulated accessibility of the NES may be important for many proteins that must stay in the nucleus until signalled to exit, for instance MapKapK2 (Meng,2002). Regulation of nuclear export may be more sophisticated than for import: one indication is that CRM1 is much more flexible and dynamic (and harder to crystallise without accessory proteins such as RAN) than importins, although being composed of similar HEAT repeat elements.