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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Kapbeta2 (also called transportin) recognizes PY nuclear localization signal (NLS), a new class of NLS with a R/H/Kx((2-5))PY motif. Here we show that Kapbeta2 complexes containing hydrophobic and basic PY-NLSs, as classified by the composition of an additional N-terminal motif, converge in structure only at consensus motifs, which explains ligand diversity. On the basis of these data and complementary biochemical analyses, we designed a Kapbeta2-specific nuclear import inhibitor, M9M.
Structure-based design of a pathway-specific nuclear import inhibitor.,Cansizoglu AE, Lee BJ, Zhang ZC, Fontoura BM, Chook YM Nat Struct Mol Biol. 2007 May;14(5):452-4. Epub 2007 Apr 15. PMID:17435768[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
- ↑ Cansizoglu AE, Lee BJ, Zhang ZC, Fontoura BM, Chook YM. Structure-based design of a pathway-specific nuclear import inhibitor. Nat Struct Mol Biol. 2007 May;14(5):452-4. Epub 2007 Apr 15. PMID:17435768 doi:http://dx.doi.org/10.1038/nsmb1229
