| In contrast , the unique insert of exon 3 in the N terminal domain of Smad 2 prevents its association with importin beta 1 . 3 ) Nuclear import of Smad 3 in vivo requires the action of the Ran GTPase , which mediates release of Smad 3 from the complex with importin beta 1 . 4 ) Importin beta 1 , Ran , and p10 / NTF2 are sufficient to mediate import of activated Smad 3 . ^^^ |