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| | <StructureSection load='2z5m' size='340' side='right'caption='[[2z5m]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='2z5m' size='340' side='right'caption='[[2z5m]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2z5m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z5M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2z5m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z5M FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qbk|1qbk]], [[2h4m|2h4m]], [[2ot8|2ot8]], [[2z5j|2z5j]], [[2z5k|2z5k]], [[2z5n|2z5n]], [[2z5o|2z5o]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2z5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z5m OCA], [https://pdbe.org/2z5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z5m RCSB], [https://www.ebi.ac.uk/pdbsum/2z5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z5m ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2z5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z5m OCA], [https://pdbe.org/2z5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z5m RCSB], [https://www.ebi.ac.uk/pdbsum/2z5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z5m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TNPO1_HUMAN 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.<ref>PMID:8986607</ref> <ref>PMID:9687515</ref> <ref>PMID:11682607</ref> <ref>PMID:19124606</ref> [[https://www.uniprot.org/uniprot/NXF1_HUMAN NXF1_HUMAN]] Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.<ref>PMID:9660949</ref> <ref>PMID:19165146</ref>
| + | [https://www.uniprot.org/uniprot/TNPO1_HUMAN 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.<ref>PMID:8986607</ref> <ref>PMID:9687515</ref> <ref>PMID:11682607</ref> <ref>PMID:19124606</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hashimoto, H]] | + | [[Category: Hashimoto H]] |
| - | [[Category: Hidaka, Y]] | + | [[Category: Hidaka Y]] |
| - | [[Category: Imamoto, N]] | + | [[Category: Imamoto N]] |
| - | [[Category: Imasaki, T]] | + | [[Category: Imasaki T]] |
| - | [[Category: Kose, S]] | + | [[Category: Kose S]] |
| - | [[Category: Sato, M]] | + | [[Category: Sato M]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Shimizu T]] |
| - | [[Category: Yamada, M]] | + | [[Category: Yamada M]] |
| - | [[Category: Exportin]]
| + | |
| - | [[Category: Importin]]
| + | |
| - | [[Category: Karyopherin]]
| + | |
| - | [[Category: Nl]]
| + | |
| - | [[Category: Nuclear transport]]
| + | |
| - | [[Category: Nucleocytoplasmic]]
| + | |
| - | [[Category: Tap]]
| + | |
| - | [[Category: Transport protein-rna binding protein complex]]
| + | |
| 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
Transportin 1 (Trn1) is a transport receptor that transports substrates from the cytoplasm to the nucleus through nuclear pore complexes by recognizing nuclear localization signals (NLSs). Here we describe four crystal structures of human Trn1 in a substrate-free form as well as in the complex with three NLSs (hnRNP D, JKTBP, and TAP, respectively). Our data have revealed that (1) Trn1 has two sites for binding NLSs, one with high affinity (site A) and one with low affinity (site B), and NLS interaction at site B controls overall binding affinity for Trn1; (2) Trn1 recognizes the NLSs at site A followed by conformational change at site B to interact with the NLSs; and (3) a long flexible loop, characteristic of Trn1, interacts with site B, thereby displacing transport substrate in the nucleus. These studies provide deep understanding of substrate recognition and dissociation by Trn1 in import pathways.
Structural basis for substrate recognition and dissociation by human transportin 1.,Imasaki T, Shimizu T, Hashimoto H, Hidaka Y, Kose S, Imamoto N, Yamada M, Sato M Mol Cell. 2007 Oct 12;28(1):57-67. PMID:17936704[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
- ↑ Imasaki T, Shimizu T, Hashimoto H, Hidaka Y, Kose S, Imamoto N, Yamada M, Sato M. Structural basis for substrate recognition and dissociation by human transportin 1. Mol Cell. 2007 Oct 12;28(1):57-67. PMID:17936704 doi:http://dx.doi.org/10.1016/j.molcel.2007.08.006
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