Fig. 3. PTEN motifs involved in nucleo-cytoplasmic shuttling. PTEN consists primarily of two domains: the phosphatase and C-terminal domains. The phosphatase domain consists of residues 1-185, with its core motif (green) spanning residues 124-130. The C-terminal domain, residues 186-403, contains the lipid-binding C2 domain (residues 186-351), two PEST sequences involved in protein stability (residues 350-375 and 379-396) and a PDZ domain (shown in red), which is involved in protein-protein interactions. A putative cytoplasmic localization signal (CLS) spans residues 19-25. Four separate non-classical NLS motifs (NLS1 to NLS4) involved in binding to and the import by MVP have been localized to residues 10-14 (RNKRR), 160-164 (RTRDKK), 233-237 (RREDK) and 265-269 (KKDK). A mono-ubiquitylation site is present at K289 and regulates nuclear localization, as does a stretch of serine and threonine phosphorylation sites: S370, S380, T382, T383 and S385 (asterisks).