A short peptide at the C terminus is responsible for the nuclear localization of RAG2.
The RAG1 and RAG2 proteins are the lymphoid-specific factors essential for V(D)J recombination, the process that leads to the diversification of antigen receptors on B and T lymphocytes. Nucleolar/nuclear localization of RAG1 is mediated by four basic domains, which are the binding sites for the nuclear transport proteins SRP1 and RCH1, and by a nuclear localization signal (NLS) in the fifth basic domain. The C-terminal region of RAG2 from amino acids (aa) 417 to 484 shows a homology with the PHD domain of other proteins involved in chromatin-mediated gene regulation by protein-protein interactions. Mutations in this domain were shown to be responsible for several diseases and in some case lead to altered subcellular localization of proteins. We found that the C-terminal PHD domain of RAG2 is not responsible for the nuclear localization of the protein. We report here the characterization of a region (aa 491-527) in the C-terminal domain of RAG2, downstream of the putative PHD domain, which directs the nuclear localization of the protein.
Corneo
Barbara
B
Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Benmerah
Alexandre
A
Villartay
Jean-Pierre de
JP
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C486206:EPS15 protein, human; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; C499311:RAG2 protein, human; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D049452:Green Fluorescent Proteins