A nuclear localization signal is an aminoalkanoic acid sequence that contains a protein for import into the nucleus by nuclear transport. Typically, this signal consists of 1 or more short sequences of charged lysines or arginines exposed on the protein surface. Different nuclear-localized proteins may share an equivalent NLS. An NLS has the other function of a nuclear export signal (NES), which targets proteins out of the nucleus. The nuclear envelope consists of concentric membranes, the outer and therefore the inner membrane. The inner and outer membranes connect at multiple sites, forming channels between the cytoplasm and therefore the nucleoplasm. These channels are covered by nuclear pore complexes (NPCs), complex multiprotein structures that mediate the transport across the nuclear membrane.
A protein translated with an NLS will bind to importin (aka karyopherin), and, together, the complex will move through the nuclear pore. At now, Ran-GTP will bind to the importin-protein complex, and its binding will cause the importin to lose affinity for the protein. The protein is released, and now the Ran-GTP/importin complex will withdraw out of the nucleus through the nuclear pore. A GTPase-activating protein within the cytoplasm that hydrolyzes the Ran-GTP to GDP and this causes a conformational change in Ran, ultimately reducing its affinity for importin. Importin is released and Ran-GDP is recycled to the nucleus where a Guanine nucleotide exchange factor (GEF) exchanges its GDP back for GTP.