<p>Karyopherins are a group of proteins involved in transporting molecules through the pores of the nuclear envelope. Karyopherins, which may act as importins or exportins, are part of the Importin-beta super-family, which all share a similar three-dimensional structure.</p><p>Members of the importin-beta (karyopherin-beta) family can bind and transport cargo by themselves, or can form heterodimers with importin-alpha. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Importin-beta is a helicoidal molecule constructed from 19 HEAT repeats. Many nuclear pore proteins contain FG sequence repeats that can bind to HEAT repeats within importins [<cite idref="PUB00009772"/>, <cite idref="PUB00034678"/>], which is important for importin-beta mediated transport.</p><p>Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. As a result, the N-terminal auto-inhibitory region on importin-alpha is free to loop back and bind to the major NLS-binding site, causing the cargo to be released [<cite idref="PUB00034676"/>]. There are additional release factors as well.</p><p>This entry represents the N-terminal domain of karyopherins that is important for the binding of the Ran protein [<cite idref="PUB00018160"/>].</p><p>More information about these proteins can be found at Protein of the Month: Importins [<cite idref="PUB00034677"/>].</p> Importin-beta, N-terminal