Alternative titles; symbols
HGNC Approved Gene Symbol: TNPO1
Cytogenetic location: 5q13.2 Genomic coordinates (GRCh38): 5:72,816,661-72,914,388 (from NCBI)
Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the protein's nuclear localization signal (NLS) and the importin, or karyopherin, receptor complex. An importin heterodimer recognizes the NLS protein in the cytoplasm via its alpha subunit and, via its beta subunit, docks the complex to a subset of peptide repeat-containing proteins known as nucleoporins. See importin beta-1 (KPNB1; 602738). Michael et al. (1995) determined that the C terminus of HNRNPA1 (164017) contains a 38-amino acid domain, termed M9, that confers bidirectional transport across the nuclear envelope. Pollard et al. (1996) found that M9-mediated nuclear import occurs by a novel pathway independent of the importin-mediated NLS pathway. Using a yeast 2-hybrid system, they identified a HeLa cell cDNA encoding a protein that interacts with an M9-containing sequence. The predicted 890-amino acid protein was designated M9-interacting protein (MIP1), or transportin. Transportin contains 2 leucine zipper motifs and a 19-amino acid highly acidic domain, and has an estimated pI of 4.6. Pollard et al. (1996) demonstrated that transportin mediated the nuclear import of M9-bearing proteins.
Bonifaci et al. (1997) isolated cDNAs encoding transportin, which they designated karyopherin beta-2, or KPNB2. They reported that the predicted protein sequence is 34% identical to that of the yeast beta-karyopherin Kap104p. Using overlay blots, Bonifaci et al. (1997) demonstrated that KPNB2 also functions as a docking factor that binds to peptide repeat-containing nucleoporins. In an assay using permeabilized HeLa cells, KPNB2 inhibited KPNB1-mediated import of an NLS-containing substrate and KPNB1 inhibited KPNB2-mediated import of recombinant HNRNPA1. These results led Bonifaci et al. (1997) to suggest that the distinct KPNB1- and KPNB2-mediated nuclear import pathways merge at least partially at the level of docking to nucleoporins.
The International Radiation Hybrid Mapping Consortium mapped the KPNB2 gene to chromosome 5 (WI-13973).
Crystal Structure
Lee et al. (2003) showed the crystal structure of importin-beta complexed with the active form of SREBP2 (600481). Importin-beta uses characteristic long helices like a pair of chopsticks to interact with an SREBP2 dimer. Importin-beta changes its conformation to reveal a pseudo-2-fold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule.
Bonifaci, N., Moroianu, J., Radu, A., Blobel, G. Karyopherin beta-2 mediates nuclear import of a mRNA binding protein. Proc. Nat. Acad. Sci. 94: 5055-5060, 1997. [PubMed: 9144189] [Full Text: https://doi.org/10.1073/pnas.94.10.5055]
Lee, S. J., Sekimoto, T., Yamashita, E., Nagoshi, E., Nakagawa, A., Imamoto, N., Yoshimura, M., Sakai, H., Chong, K. T., Tsukihara, T., Yoneda, Y. The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science 302: 1571-1575, 2003. [PubMed: 14645851] [Full Text: https://doi.org/10.1126/science.1088372]
Michael, W. M., Choi, M., Dreyfuss, G. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell 83: 415-422, 1995. [PubMed: 8521471] [Full Text: https://doi.org/10.1016/0092-8674(95)90119-1]
Pollard, V. W., Michael, W. M., Nakielny, S., Siomi, M. C., Wang, F., Dreyfuss, G. A novel receptor-mediated nuclear protein import pathway. Cell 86: 985-994, 1996. [PubMed: 8808633] [Full Text: https://doi.org/10.1016/s0092-8674(00)80173-7]