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| | <StructureSection load='4c0o' size='340' side='right'caption='[[4c0o]], [[Resolution|resolution]] 2.56Å' scene=''> | | <StructureSection load='4c0o' size='340' side='right'caption='[[4c0o]], [[Resolution|resolution]] 2.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c0o]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C0O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c0o]] is a 4 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=4C0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C0O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=4c0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0o OCA], [https://pdbe.org/4c0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c0o RCSB], [https://www.ebi.ac.uk/pdbsum/4c0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0o ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c0p|4c0p]], [[4c0q|4c0q]]</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0o OCA], [http://pdbe.org/4c0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c0o RCSB], [http://www.ebi.ac.uk/pdbsum/4c0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F. | + | [[https://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains.<ref>PMID:10366588</ref> <ref>PMID:10713112</ref> <ref>PMID:11517331</ref> <ref>PMID:12628928</ref> [[http://www.uniprot.org/uniprot/SRSF1_HUMAN SRSF1_HUMAN]] Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.<ref>PMID:8223481</ref> <ref>PMID:8139654</ref> | + | [[https://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains.<ref>PMID:10366588</ref> <ref>PMID:10713112</ref> <ref>PMID:11517331</ref> <ref>PMID:12628928</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Transportin 3 (Tnpo3, Transportin-SR2) is implicated in nuclear import of splicing factors and HIV-1 replication. Herein, we show that the majority of cellular Tnpo3 binding partners contain arginine-serine (RS) repeat domains and present crystal structures of human Tnpo3 in its free as well as GTPase Ran- and alternative splicing factor/splicing factor 2 (ASF/SF2)-bound forms. The flexible beta-karyopherin fold of Tnpo3 embraces the RNA recognition motif and RS domains of the cargo. A constellation of charged residues on and around the arginine-rich helix of Tnpo3 HEAT repeat 15 engage the phosphorylated RS domain and are critical for the recognition and nuclear import of ASF/SF2. Mutations in the same region of Tnpo3 impair its interaction with the cleavage and polyadenylation specificity factor 6 (CPSF6) and its ability to support HIV-1 replication. Steric incompatibility of the RS domain and RanGTP engagement by Tnpo3 provides the mechanism for cargo release in the nucleus. Our results elucidate the structural bases for nuclear import of splicing factors and the Tnpo3-CPSF6 nexus in HIV-1 biology.
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| - | | + | |
| - | Structural basis for nuclear import of splicing factors by human Transportin 3.,Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P Proc Natl Acad Sci U S A. 2014 Jan 21. PMID:24449914<ref>PMID:24449914</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4c0o" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Importin|Importin]] | + | *[[Importin 3D structures|Importin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cherepanov, P]] | + | [[Category: Cherepanov P]] |
| - | [[Category: Cook, N J]] | + | [[Category: Cook NJ]] |
| - | [[Category: Maertens, G N]] | + | [[Category: Maertens GN]] |
| - | [[Category: Heat repeat]]
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| - | [[Category: Nuclear import]]
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| - | [[Category: Rrm domain]]
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| - | [[Category: Rs domain]]
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| - | [[Category: Splicing factor]]
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| - | [[Category: Transport protein-rna binding protein complex]]
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