Nuclear and ER Import

For proteins to get into the nucleus, it requires a Nuclear Localization Sequence (NLS). This NLS has a chain of positive amino acids in the sequence that the nuclear pore complex can recognize and let the protein through to the inside of the nucleus. To let it in, the protein with the NLS, importin Alpha and Beta bind to it. Once in the nucleus, RAN GTP binds to importin and importin Beta leaves the protein with the NLS. Some proteins that are less than 50kDa to pass through the nuclear membrane through diffusion. Also, in the nuclear import, the signal sequence is not removed and the protein does not need to be unfolded. 

For the transport into the ER, a long sequence of hydrophobic amino acids are required. When the protein travels to the ER for import, the signal sequence is cleaved off and the protein unfolds. Once in the ER lumen, it refolds but the protein is shorter since the signal was clipped off.