The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import

EMBO J. 1996 Apr 15;15(8):1818-25.


Nuclear proteins are targeted through the nuclear pore complex (NPC) in an energy-dependent reaction. The import reaction is mediated by nuclear localization sequences (NLS) in the substrate which are recognized by heterodimeric cytoplasmic receptors. hSRP1 alpha is an NLS-binding subunit of the human NLS receptor complex and is complexed in vivo with a second subunit of 97 kDa (p97). We show here that a short amino-terminal domain in hSRP1 alpha is necessary and sufficient for its interaction with p97. This domain is conserved in other SRP1-like proteins and its fusion to a cytoplasmic reporter protein is sufficient to promote complete nuclear import, circumventing the usual requirement for an NLS receptor interaction. The same amino-terminal domain inhibits import of NLS-containing proteins when added to an in vitro nuclear transport assay. While full-length hSRP alpha is able to leave the nucleus, the amino-terminal domain alone is not sufficient to promote exit. We conclude that hSRP1 alpha functions as an adaptor to tether NLS-containing substrates to the protein import machinery.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites / genetics
  • Biological Transport, Active
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Conserved Sequence
  • Cytoplasm / metabolism
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Escherichia coli / genetics
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Molecular Structure
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid


  • DNA Primers
  • DNA, Complementary
  • NOLC1 protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • nuclear protein import factor p97

Associated data

  • GENBANK/D45836
  • GENBANK/L38644
  • GENBANK/L38951
  • GENBANK/L39793
  • GENBANK/T05916
  • GENBANK/T07554
  • GENBANK/T09278