The importin β binding domain as a master regulator of nucleocytoplasmic transport

Biochim Biophys Acta. 2011 Sep;1813(9):1578-92. doi: 10.1016/j.bbamcr.2010.10.012. Epub 2010 Oct 26.


Specific and efficient recognition of import cargoes is essential to ensure nucleocytoplasmic transport. To this end, the prototypical karyopherin importin β associates with import cargoes directly or, more commonly, through import adaptors, such as importin α and snurportin. Adaptor proteins bind the nuclear localization sequence (NLS) of import cargoes while recruiting importin β via an N-terminal importin β binding (IBB) domain. The use of adaptors greatly expands and amplifies the repertoire of cellular cargoes that importin β can efficiently import into the cell nucleus and allows for fine regulation of nuclear import. Accordingly, the IBB domain is a dedicated NLS, unique to adaptor proteins that functions as a molecular liaison between importin β and import cargoes. This review provides an overview of the molecular role played by the IBB domain in orchestrating nucleocytoplasmic transport. Recent work has determined that the IBB domain has specialized functions at every step of the import and export pathway. Unexpectedly, this stretch of ~40 amino acids plays an essential role in regulating processes such as formation of the import complex, docking and translocation through the nuclear pore complex (NPC), release of import cargoes into the cell nucleus and finally recycling of import adaptors and importin β into the cytoplasm. Thus, the IBB domain is a master regulator of nucleocytoplasmic transport, whose complex molecular function is only recently beginning to emerge. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Evolution, Molecular
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / genetics
  • Nuclear Localization Signals / physiology
  • Phylogeny
  • Protein Interaction Domains and Motifs
  • RNA Cap-Binding Proteins / chemistry
  • RNA Cap-Binding Proteins / genetics
  • RNA Cap-Binding Proteins / physiology
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Signal Transduction / physiology
  • beta Karyopherins / chemistry*
  • beta Karyopherins / genetics
  • beta Karyopherins / physiology*


  • Nuclear Localization Signals
  • RNA Cap-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • SNUPN protein, human
  • beta Karyopherins