InterPro: IPR002075 Nuclear transport factor 2

Ran (IPR002041) is an evolutionary conserved member of the Ras superfamily of small GTPases that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Import receptors bind their cargos in the cytoplasm where the concentration of RanGTP is low and release their cargos in the nucleus where the concentration of RanGTP is high [1]. Export receptors respond to Ran GTP in the opposite manner.

Nuclear transport factor 2 (NTF2) is a homodimer of approximately 14kDa subunits which stimulates efficient nuclear import of a cargo protein. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins. NTF2 binds to RanGDP sufficiently strongly for the complex to remain intact during transport through NPCs, but the interaction between NTF2 and FxFG nucleoporins is much more transient, which would enable NTF2 to move through the NPC by hopping from one repeat to another [2, 3].

NTF2 folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues. RanGDP binds to NTF2 by inserting a conserved phenylalanine residue into the hydrophobic pocket of NTF2 and making electrostatic interactions with the conserved negatively charged residues that surround the cavity.

A structurally similar domain appears in other nuclear import proteins.