Where can the nuclear localization signal (NLS) be located on a protein?

The nuclear localization signal (NLS) is critical for the transport of proteins into the nucleus and can indeed be located anywhere within the protein sequence. This flexibility allows for various configurations and functionalities in different proteins, effectively enabling them to be recognized by the nuclear transport machinery regardless of where the NLS is situated.

For example, some proteins may have their NLS near the N-terminus, while others may have it closer to the C-terminus or embedded within the protein's central region. This versatility is essential, as the protein's overall structure, folding, and functional context can influence its interaction with import receptors that mediate nuclear transport. Hence, the ability of the NLS to be positioned throughout the protein supports the diverse roles proteins play in cellular processes and their unique trafficking needs.