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| | <StructureSection load='6gx9' size='340' side='right'caption='[[6gx9]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6gx9' size='340' side='right'caption='[[6gx9]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gx9]] is a 4 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=6GX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GX9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gx9]] 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=6GX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GX9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.7Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNPO3, IPO12 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CPSF6, CFIM68 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6gx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gx9 OCA], [https://pdbe.org/6gx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gx9 RCSB], [https://www.ebi.ac.uk/pdbsum/6gx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gx9 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=6gx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gx9 OCA], [https://pdbe.org/6gx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gx9 RCSB], [https://www.ebi.ac.uk/pdbsum/6gx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gx9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://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 == |
| - | [[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> [[https://www.uniprot.org/uniprot/CPSF6_HUMAN CPSF6_HUMAN]] Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping.<ref>PMID:9659921</ref> <ref>PMID:8626397</ref> <ref>PMID:14690600</ref> <ref>PMID:20695905</ref> <ref>PMID:21295486</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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6gx9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6gx9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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]] | + | [[Category: Cook N]] |
| - | [[Category: Karyopherin-cargo complex]]
| + | |
| - | [[Category: Nuclear import]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Sr-like domain]]
| + | |
| Structural highlights
Disease
TNPO3_HUMAN Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F.
Function
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.[1] [2] [3] [4]
Publication Abstract from PubMed
Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor 5 (CPSF5) and serine/arginine-like protein CPSF6, regulates alternative polyadenylation (APA). Loss of CFIm function results in proximal polyadenylation site usage, shortening mRNA 3' untranslated regions (UTRs). Although CPSF6 plays additional roles in human disease, its nuclear translocation mechanism remains unresolved. Two beta-karyopherins, transportin (TNPO) 1 and TNPO3, can bind CPSF6 in vitro, and we demonstrate here that while the TNPO1 binding site is dispensable for CPSF6 nuclear import, the arginine/serine (RS)-like domain (RSLD) that mediates TNPO3 binding is critical. The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm. Although hypophosphorylated CPSF6 largely supported normal polyadenylation site usage, a significant number of mRNAs harbored unnaturally extended 3' UTRs, similar to what is observed when other APA regulators, such as CFIIm component proteins, are depleted. Our results clarify the mechanism of CPSF6 nuclear import and highlight differential roles for RSLD phosphorylation in nuclear translocation versus regulation of APA.
Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6.,Jang S, Cook NJ, Pye VE, Bedwell GJ, Dudek AM, Singh PK, Cherepanov P, Engelman AN Nucleic Acids Res. 2019 Mar 27. pii: 5420532. doi: 10.1093/nar/gkz206. PMID:30916345[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kataoka N, Bachorik JL, Dreyfuss G. Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol. 1999 Jun 14;145(6):1145-52. PMID:10366588
- ↑ Lai MC, Lin RI, Huang SY, Tsai CW, Tarn WY. A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem. 2000 Mar 17;275(11):7950-7. PMID:10713112
- ↑ Lai MC, Lin RI, Tarn WY. Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10154-9. Epub 2001 Aug 21. PMID:11517331 doi:http://dx.doi.org/10.1073/pnas.181354098
- ↑ Lai MC, Kuo HW, Chang WC, Tarn WY. A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 2003 Mar 17;22(6):1359-69. PMID:12628928 doi:http://dx.doi.org/10.1093/emboj/cdg126
- ↑ Jang S, Cook NJ, Pye VE, Bedwell GJ, Dudek AM, Singh PK, Cherepanov P, Engelman AN. Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6. Nucleic Acids Res. 2019 Mar 27. pii: 5420532. doi: 10.1093/nar/gkz206. PMID:30916345 doi:http://dx.doi.org/10.1093/nar/gkz206
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