Nuclear localization signals for four distinct karyopherin-β nuclear import systems

Biochem J. 2015 Jun 15;468(3):353-62. doi: 10.1042/BJ20150368.


The Karyopherin-β family of proteins mediates nuclear transport of macromolecules. Nuclear versus cytoplasmic localization of proteins is often suggested by the presence of NLSs (nuclear localization signals) or NESs (nuclear export signals). Import-Karyopherin-βs or Importins bind to NLSs in their protein cargos to transport them through nuclear pore complexes into the nucleus. Until recently, only two classes of NLS had been biochemically and structurally characterized: the classical NLS, which is recognized by the Importin-α/β heterodimer and the PY-NLS (proline-tyrosine NLS), which is recognized by Karyopherin-β2 or Transportin-1. Structures of two other Karyopherin-βs, Kap121 and Transportin-SR2, in complex with their respective cargos were reported for the first time recently, revealing two new distinct classes of NLSs. The present paper briefly describes the classical NLS, reviews recent literature on the PY-NLS and provides in-depth reviews of the two newly discovered classes of NLSs that bind Kap121p and Transportin-SR respectively.

Keywords: Importin; Karyopherin; nuclear import; nuclear localization signal (NLS); nuclear pore; nucleocytoplasmic transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Nucleus / metabolism*
  • Humans
  • Models, Biological*
  • Nuclear Export Signals
  • Nuclear Localization Signals*
  • Protein Conformation
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • beta Karyopherins / chemistry
  • beta Karyopherins / metabolism*


  • Nuclear Export Signals
  • Nuclear Localization Signals
  • Protein Isoforms
  • Saccharomyces cerevisiae Proteins
  • beta Karyopherins