Structural highlights
Function
[TNPO1_HUMAN] Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Appears also to be involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones, and SRP19. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Mediates nuclear import of ADAR/ADAR1 (isoform 5) in a RanGTP-dependent manner.[1] [2] [3] [4]
Publication Abstract from PubMed
Karyopherin-beta2 or Transportin-1 binds proline-tyrosine nuclear localization signals (PY-NLSs) in its cargos. PY-NLSs are described by structural disorder, overall positive charge, and binding epitopes composed of an N-terminal hydrophobic or basic motif and a C-terminal R-X2-5P-Y motif. The N-terminal tail of histone H3 binds Kapbeta2 with high affinity but does not contain a recognizable PY-NLS. The crystal structure of the Kapbeta2-H3 tail shows residues 11-27 of H3 binding to the PY-NLS site of Kapbeta2. H3 residues 11TGGKAPRK18 bind the site for PY-NLS Epitope 1 (N-terminal hydrophobic/basic motif), which is most important for Kapbeta2-binding. H3 residue Arg26 occupies the PY-NLS Epitope 2 position (usually arginine of R-X2-5P-Y) but PY-NLS Epitope 3 (proline-tyrosine motif) is missing in the H3 tail. Histone H3 thus provides an example of a PY-NLS variant with no proline-tyrosine or homologous proline-hydrophobic motif. The H3 tail uses a very strong Epitope 1 to compensate for loss of the often-conserved proline-tyrosine epitope.
Karyopherin-beta2 Recognition of a PY-NLS Variant that Lacks the Proline-Tyrosine Motif.,Soniat M, Chook YM Structure. 2016 Sep 7. pii: S0969-2126(16)30230-1. doi:, 10.1016/j.str.2016.07.018. PMID:27618664[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakielny S, Siomi MC, Siomi H, Michael WM, Pollard V, Dreyfuss G. Transportin: nuclear transport receptor of a novel nuclear protein import pathway. Exp Cell Res. 1996 Dec 15;229(2):261-6. PMID:8986607 doi:10.1006/excr.1996.0369
- ↑ Jakel S, Gorlich D. Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J. 1998 Aug 3;17(15):4491-502. PMID:9687515 doi:10.1093/emboj/17.15.4491
- ↑ Dean KA, von Ahsen O, Gorlich D, Fried HM. Signal recognition particle protein 19 is imported into the nucleus by importin 8 (RanBP8) and transportin. J Cell Sci. 2001 Oct;114(Pt 19):3479-85. PMID:11682607
- ↑ Fritz J, Strehblow A, Taschner A, Schopoff S, Pasierbek P, Jantsch MF. RNA-regulated interaction of transportin-1 and exportin-5 with the double-stranded RNA-binding domain regulates nucleocytoplasmic shuttling of ADAR1. Mol Cell Biol. 2009 Mar;29(6):1487-97. doi: 10.1128/MCB.01519-08. Epub 2009 Jan, 5. PMID:19124606 doi:10.1128/MCB.01519-08
- ↑ Soniat M, Chook YM. Karyopherin-beta2 Recognition of a PY-NLS Variant that Lacks the Proline-Tyrosine Motif. Structure. 2016 Sep 7. pii: S0969-2126(16)30230-1. doi:, 10.1016/j.str.2016.07.018. PMID:27618664 doi:http://dx.doi.org/10.1016/j.str.2016.07.018
