Schematic representation of four distinct mechanisms by which phosphorylation can up-regulate importin β1-dependent nuclear import. (A) Phosphorylation within the NLS of EBNA-1 enhances the binding affinity for importin α5. (B) Phosphorylation of the HBV core antigen causes a conformational change that positions the NLS on the exterior of the capsid, and hence promotes its nuclear import. (C) Phosphorylation of serines upstream of the NLS of SV40 large T-antigen enhances nuclear import likely by enhancing the cargo recognition by importin α1. (D) Phosphorylation of STAT1 at Tyr701 induces a conformational rearrangement that exposes a non-classical dsNLS that is bound specifically and with high affinity by importin α5. In all diagrams, import cargos and importin β1 are colored in cyan and blue, respectively while importin α1 is in green and α5 in violet. The NLS is depicted as a yellow flag and the phosphorylation site, or the kinase responsible for phosphorylation, is in red.