Nuclear localization signal sequence

Importins are transport proteins at the nuclear pore complex, needed for the selective import of proteins into the nucleus. They recognize nuclear localization signal sequences of cargo proteins. 

Figure 12.38. Movement of a Protein Into the Nucleus. Localization of (A) unmodified pyruvate kinase, and (B) pyruvate kinase containing a nuclear localization signal sequence attached to its amino terminus. The protein was visualized hy fluorescence microscopy after staining with a specific antibody. [From W. D. Richardson, B. L. Roberts, and A. E. Smith. Cell 44(1986) 79.]...

B) pyruvate kinase containing a nuclear localization signal sequence attached to its amino terminus. The protein was visualized by fluorescence miaoscopy after staining with a specific antibody. 

Sequence of amino acids that determine the transport of proteins into the nucleus. Although there is no clear consensus, nuclear localization signals tend to be rich in positively charged residues, which allow interaction with proteins from the nuclear import machinery (i.e., importins). 

NLS, nuclear localization signal PTS, peroxisomal-matrix targeting sequence. 

Figure 2. Structural and functional domains of PARP-1. PARP-1 has a highly conserved structural and functional organization including (1) an N-terminal DNA binding domain with two Cys-Cys-His-Cys zinc finger motifs (FI and Fll), (2) a nuclear localization signal (NLS), (3) a central automodification domain containing a BRCT ( BRCAl C-terminus-like ) protein-protein interaction motif, and (4) a C-terminal catalytic domain with a contiguous 50 amino acid sequence, the PARP signature motif, that forms the active site...

This enzyme is also known to be phosphorylated and translocated to the nucleus in a cell cycle-dependent fashion. Since only phosphorylated form of El is translocated to the nucleus despite the presence of the nuclear localization signal in the El sequence, it is conceivable that phosphorylation is an obligatory additional signal for nuclear localization. Evidence obtained by Stephen et shows that phosphorylation facilitates either transport to the nucleus or its retention in the nucleus. 

The nuclear envelope is perforated with huge macromolecular assemblies of 30 different proteins that form nuclear pore complexes with a central channel of 25-30 nm in diameter. This channel allows proteins smaller than 30 kDa to passively traverse the outer and inner nuclear membranes. Larger proteins are actively transported across the nuclear envelope and contain nuclear localization signal (NLS) sequence motifs. These signals consist of one or two clusters of four or five basic residues localized usually within the polypeptide chain. The import of proteins with NLS through the channel is facilitated by the carrier heterodimer of importin-a ( > (Gorlich and Kutay 1999 Pemberton and Paschal... 

Although most protein synthesis occurs in the cytoplasm of eukaryotic cells, many proteins are destined to perform their functions within specific cellular organelles. Such proteins usually contain amino acid sequences that direct these proteins to their final locations. For example, nuclear proteins contain a "nuclear localization signal," whereas mitochondrial proteins have a "mitochondrial entry sequence."... 

The mouse Dtnbpl transcript identified as a on AceView is predicted to encode a protein of 408 aa, which is 56 aa longer than the largest mouse dysbindin-1A isoform reported in the literature (i.e., the 352 aa isoform of Benson et al., 2001). If we accept the first ATG in transcript a as the start codon, the predicted protein matches the 352 aa isoform. AceView instead lists the longer possibility for two reasons. Near the 5 end of the transcript is a less common start codon sequence (CTG). Between the 5 end and the first ATG sequence are 168 nucleotides potentially encoding an arginine-proline rich N-terminal extension that may serve as a nuclear localization signal of functional interest. Indeed, the 408 aa variant of dysbindin-1 A has been predicted in mouse undifferentiated limb mesenchyme (NCBI accession no. AAH48682). But it is not predicted elsewhere. In most tissues, then, transcript a is probably translated as the 352 aa isoform. 

Malek S, Huxford T, Ghosh G (1998) Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB. J Biol Chem 273 25427-25435... 

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