NEScontaining

NEScontaining is a descriptor used in molecular biology to label proteins that contain a Nuclear Export Signal, a short linear sequence that mediates export from the nucleus to the cytoplasm. In most cases, export is mediated by the export receptor CRM1 (XPO1) in a complex with Ran-GTP, enabling transit through the nuclear pore complex. This mechanism helps regulate the subcellular distribution of many proteins, coordinating responses to cellular signals and stress.

Classical NES motifs are typically leucine-rich and recognized by CRM1. A common conceptual pattern is a hydrophobic-residue-rich sequence arranged with specific spacing, often summarized as a leucine-rich motif such as L-x(2-3)-L-x(2-3)-L-x-L, though many NESs do not fit a single rigid consensus. Noncanonical NES signals exist as well, and some proteins contain multiple or overlapping export sequences. The functional NES is often identified by showing CRM1 dependency and cytoplasmic accumulation upon disruption of export.

Prediction methods exist to identify potential NESs in protein sequences, including bioinformatics tools such as NetNES and LocNES, but experimental validation is typically required. Validation approaches include site-directed mutagenesis of hydrophobic residues to disrupt export, localization assays in cells, and the use of CRM1 inhibitors (for example, leptomycin B) to confirm CRM1-dependent export.

NES-containing proteins encompass both cellular regulators and viral factors. Examples include HIV-1 Rev and the tumor suppressor p53, whose nuclear-cytoplasmic balance is modulated in response to cellular conditions. Misregulation of NES-dependent export has been linked to cancer and other diseases, making CRM1-mediated export a target of therapeutic investigation.