BACKGROUND: Nuclear translocation of large proteins is mediated through specific 
protein carriers, collectively named karyopherins (importins, exportins and 
adaptor proteins). Cargo proteins are recognized by importins through specific 
motifs, known as nuclear localization signals (NLS). However, only the NLS 
recognized by importin α and transportin (M9 NLS) have been identified so far 
METHODS: An unsupervised in silico approach was used, followed by experimental 
validation.
RESULTS: We identified the sequence EKRKI(E/R)(K/L/R/S/T) as an NLS signal for 
importin 7 recognition. This sequence was validated in the breast cancer cell 
line T47D, which expresses importin 7. Finally, we verified that importin 
7-mediated nuclear protein transport is affected by cargo protein 
phosphorylation.
CONCLUSIONS: The NLS sequence for importin 7 was identified and we propose this 
approach as an identification method of novel specific NLS sequences for 
β-karyopherin family members.
GENERAL SIGNIFICANCE: Elucidating the complex relationships of the nuclear 
transporters and their cargo proteins may help in laying the foundation for the 
development of novel therapeutics, targeting specific importins, with an 
immediate translational impact.