Diversification of importin-α isoforms in cellular trafficking and disease states

Biochem J. 2015 Feb 15;466(1):13-28. doi: 10.1042/BJ20141186.


The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Animals
  • Cell Nucleus / metabolism*
  • Cell Nucleus / virology
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Humans
  • Models, Molecular
  • Nuclear Localization Signals
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Signal Transduction
  • Viral Proteins / metabolism*
  • Virus Diseases / genetics
  • Virus Diseases / metabolism*
  • Virus Diseases / virology
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*


  • Nuclear Localization Signals
  • Protein Isoforms
  • Viral Proteins
  • alpha Karyopherins