[1] Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface.
[1] An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus.
[4] Rotello et al. compared the nuclear localization efficiencies of eGFP fused NLSs of SV40 Large T-Antigen, nucleoplasmin (AVKRPAATKKAGQAKKKKLD), EGL-13 (MSRRRKANPTKLSENAKKLAKEVEN), c-Myc (PAAKRVKLD) and TUS-protein (KLKIKRPVK) through rapid intracellular protein delivery.
[5] There are many other types of NLS, such as the acidic M9 domain of hnRNP A1, the sequence KIPIK in yeast transcription repressor Matα2, and the complex signals of U snRNPs.
[6] A signal that appears to be specific for the massively produced and transported ribosomal proteins,[7][8] seems to come with a specialized set of importin β-like nuclear import receptors.
These experiments were part of a series that subsequently led to studies of nuclear reprogramming, directly relevant to stem cell research.
In fact, only a small percentage of cellular (non-viral) nuclear proteins contained a sequence similar to the SV40 NLS.
A detailed examination of nucleoplasmin identified a sequence with two elements made up of basic amino acids separated by a spacer arm.
A protein translated with an NLS will bind strongly to importin (aka karyopherin), and, together, the complex will move through the nuclear pore.
A GTPase-activating protein (GAP) in the cytoplasm hydrolyzes the Ran-GTP to GDP, and this causes a conformational change in Ran, ultimately reducing its affinity for importin.