Sam68, a nuclear RNA binding protein, binds to Src and is phosphorylated at tyrosine residues in an M-phase specific manner, Here we identified a stretch of 24 amino acid residues in the COOH-terminal portion of Sam68 which function as a nuclear localization signal, This signal sequence bears no apparent homology to any other known nuclear localization sequence, However, this sequence was found to contain a motif, PPXXR (P, Pro; R, Arg), which is conserved in various RNA binding proteins including hnRNP proteins, Replacement of Arg in this motif with Ala abolished the nuclear accumulation of a GFP fusion protein, suggesting that this residue is important in translocating the protein to the nucleus. (C) 1997 Federation of European Biochemical Societies.