Nuclear localization signal

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A nuclear localizing sequence (NLS) is an amino acid sequence which acts like a 'tag' on the exposed surface of a protein. This sequence is used to confine the protein to the cell nucleus through the Nuclear Pore Complex and to direct a newly synthesized protein into the nucleus via its recognition by cytosolic nuclear transport receptors. Typically, this signal consists of a few short sequences of positively charged lysines or arginines. Different nuclear localized proteins may share the same NLS.

Genetically the NLS results from transcription of a nuclear localizing sequence. Cellular processes and protein function may be studied by adding a known NLS sequence to a gene, confining the chimeric protein product to the nucleus. A NLS has the opposite function of a nuclear export signal, which confines proteins to the cytosolic face of the nuclear membrane. Typically the NLS will have a sequence (NH2)-Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-(COOH).

A protein translated with a NLS will bind strongly to importin, and together, the complex will move through the nuclear pore. At this point, 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 move back out of the nucleus 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. Importin is released and Ran-GDP is recycled back to the nucleus where guanine exchange factor (GEF) exchanges its GDP back for GTP.

Proteins gain entry into the nucleus through the nuclear envelope. The nuclear envelope consist of concentric membranes, the outer and the inner membrane. These are the gateways to the nucleus. The envelope consist of pores or large nuclear complexes.