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==Crystal structure of transportin-SR2, a karyopherin involved in human disease, in complex with Ran==
==Crystal structure of transportin-SR2, a karyopherin involved in human disease, in complex with Ran==
<StructureSection load='4ol0' size='340' side='right' caption='[[4ol0]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='4ol0' size='340' side='right'caption='[[4ol0]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ol0]] is a 2 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=4OL0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OL0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ol0]] 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=4OL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OL0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNPO3, IPO12 ([http://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=4ol0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ol0 OCA], [https://pdbe.org/4ol0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ol0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ol0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ol0 ProSAT]</span></td></tr>
<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=4ol0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ol0 OCA], [http://pdbe.org/4ol0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ol0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ol0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ol0 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://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/RAN_HUMAN RAN_HUMAN]] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>  Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref> [[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> 
[https://www.uniprot.org/uniprot/RAN_HUMAN RAN_HUMAN] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>  Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[GTP-binding protein|GTP-binding protein]]
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
*[[Importin|Importin]]
*[[Importin 3D structures|Importin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Strelkov, S V]]
[[Category: Large Structures]]
[[Category: Tsirkone, V G]]
[[Category: Strelkov SV]]
[[Category: Active transport]]
[[Category: Tsirkone VG]]
[[Category: Human karyopherin]]
[[Category: Nucleus]]
[[Category: Protein transport]]
[[Category: Ran gtp-binding protein]]

Revision as of 10:31, 25 January 2023

Crystal structure of transportin-SR2, a karyopherin involved in human disease, in complex with RanCrystal structure of transportin-SR2, a karyopherin involved in human disease, in complex with Ran

Structural highlights

4ol0 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RAN_HUMAN GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.[1] [2] [3] [4] Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.[5] [6] [7] [8]

Publication Abstract from PubMed

Transportin SR2 (TRN-SR2) is a beta-type karyopherin responsible for the nuclear import of specific cargoes, including serine/arginine-rich splicing factors. The protein has been implicated in a variety of human diseases, including HIV infection, primary biliary cirrhosis and limb-girdle muscular dystrophy 1F. Towards understanding its molecular mechanism, a 2.9 A resolution crystal structure of human TRN-SR2 complexed with the small GTPase Ran has been determined. TRN-SR2 is composed of 20 alpha-helical HEAT repeats forming a solenoid-like fold. The first nine repeats form a `cradle' for the binding of RanGTP, revealing similarities but also differences with respect to the related importin 13 complex.

Structure of transportin SR2, a karyopherin involved in human disease, in complex with Ran.,Tsirkone VG, Beutels KG, Demeulemeester J, Debyser Z, Christ F, Strelkov SV Acta Crystallogr F Struct Biol Commun. 2014 Jun;70(Pt 6):723-9. doi:, 10.1107/S2053230X14009492. Epub 2014 May 24. PMID:24915079[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
  2. ↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
  3. ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
  4. ↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
  5. ↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
  6. ↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
  7. ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
  8. ↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
  9. ↑ Tsirkone VG, Beutels KG, Demeulemeester J, Debyser Z, Christ F, Strelkov SV. Structure of transportin SR2, a karyopherin involved in human disease, in complex with Ran. Acta Crystallogr F Struct Biol Commun. 2014 Jun;70(Pt 6):723-9. doi:, 10.1107/S2053230X14009492. Epub 2014 May 24. PMID:24915079 doi:http://dx.doi.org/10.1107/S2053230X14009492

4ol0, resolution 2.90Å

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