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<StructureSection load='2xwu' size='340' side='right'caption='[[2xwu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='2xwu' size='340' side='right'caption='[[2xwu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xwu]] 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=2XWU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XWU FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xwu]] 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=2XWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XWU FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gro|2gro]], [[2grr|2grr]], [[1kps|1kps]], [[2grp|2grp]], [[1z5s|1z5s]], [[2x19|2x19]], [[2grq|2grq]], [[1a3s|1a3s]], [[2grn|2grn]]</td></tr>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2gro|2gro]], [[2grr|2grr]], [[1kps|1kps]], [[2grp|2grp]], [[1z5s|1z5s]], [[2x19|2x19]], [[2grq|2grq]], [[1a3s|1a3s]], [[2grn|2grn]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xwu OCA], [http://pdbe.org/2xwu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xwu RCSB], [http://www.ebi.ac.uk/pdbsum/2xwu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xwu 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=2xwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xwu OCA], [https://pdbe.org/2xwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xwu RCSB], [https://www.ebi.ac.uk/pdbsum/2xwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xwu ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UBC9_HUMAN UBC9_HUMAN]] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.<ref>PMID:8668529</ref> <ref>PMID:11451954</ref> <ref>PMID:15809060</ref> <ref>PMID:19744555</ref> <ref>PMID:19638400</ref> <ref>PMID:17466333</ref> <ref>PMID:20077568</ref>  [[http://www.uniprot.org/uniprot/IPO13_HUMAN IPO13_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). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.<ref>PMID:11447110</ref> <ref>PMID:15143176</ref>   
[[https://www.uniprot.org/uniprot/UBC9_HUMAN UBC9_HUMAN]] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.<ref>PMID:8668529</ref> <ref>PMID:11451954</ref> <ref>PMID:15809060</ref> <ref>PMID:19744555</ref> <ref>PMID:19638400</ref> <ref>PMID:17466333</ref> <ref>PMID:20077568</ref>  [[https://www.uniprot.org/uniprot/IPO13_HUMAN IPO13_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). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.<ref>PMID:11447110</ref> <ref>PMID:15143176</ref>   
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==

Revision as of 15:18, 27 April 2022

CRYSTAL STRUCTURE OF IMPORTIN 13 - UBC9 COMPLEXCRYSTAL STRUCTURE OF IMPORTIN 13 - UBC9 COMPLEX

Structural highlights

2xwu is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:Ubiquitin--protein ligase, with EC number 6.3.2.19
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBC9_HUMAN] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.[1] [2] [3] [4] [5] [6] [7] [IPO13_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). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.[8] [9]

Publication Abstract from PubMed

Importin13 (Imp13) is an unusual beta-karyopherin that is able to both import and export cargoes in and out of the nucleus. In the cytoplasm, Imp13 associates with different cargoes such as Mago-Y14 and Ubc9, and facilitates their import into the nucleus where RanGTP binding promotes the release of the cargo. In this study, we present the 2.8 A resolution crystal structure of Imp13 in complex with the SUMO E2-conjugating enzyme, Ubc9. The structure shows an uncommon mode of cargo-karyopherin recognition with Ubc9 binding at the N-terminal portion of Imp13, occupying the entire RanGTP-binding site. Comparison of the Imp13-Ubc9 complex with Imp13-Mago-Y14 shows the remarkable plasticity of Imp13, whose conformation changes from a closed ring to an open superhelix when bound to the two different cargoes. The structure also shows that the binding mode is compatible with the sumoylated states of Ubc9. Indeed, we find that Imp13 is able to bind sumoylated Ubc9 in vitro and suppresses autosumoylation activity in the complex.

Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation.,Grunwald M, Bono F EMBO J. 2010 Dec 7. PMID:21139563[10]

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

See Also

References

  1. ↑ Yasugi T, Howley PM. Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res. 1996 Jun 1;24(11):2005-10. PMID:8668529
  2. ↑ Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. PMID:11451954 doi:10.1074/jbc.M104214200
  3. ↑ Kim YE, Kim DY, Lee JM, Kim ST, Han TH, Ahn JH. Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem Biophys Res Commun. 2005 May 13;330(3):746-54. PMID:15809060 doi:10.1016/j.bbrc.2005.03.052
  4. ↑ Kuo FT, Bentsi-Barnes IK, Barlow GM, Bae J, Pisarska MD. Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene. Cell Signal. 2009 Dec;21(12):1935-44. doi: 10.1016/j.cellsig.2009.09.001. Epub, 2009 Sep 8. PMID:19744555 doi:10.1016/j.cellsig.2009.09.001
  5. ↑ Figueroa-Romero C, Iniguez-Lluhi JA, Stadler J, Chang CR, Arnoult D, Keller PJ, Hong Y, Blackstone C, Feldman EL. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 2009 Nov;23(11):3917-27. doi: 10.1096/fj.09-136630. Epub 2009 Jul 28. PMID:19638400 doi:10.1096/fj.09-136630
  6. ↑ Capili AD, Lima CD. Structure and analysis of a complex between SUMO and Ubc9 illustrates features of a conserved E2-Ubl interaction. J Mol Biol. 2007 Jun 8;369(3):608-18. Epub 2007 Apr 6. PMID:17466333 doi:10.1016/j.jmb.2007.04.006
  7. ↑ Sekiyama N, Arita K, Ikeda Y, Hashiguchi K, Ariyoshi M, Tochio H, Saitoh H, Shirakawa M. Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45. Proteins. 2009 Dec 4. PMID:20077568 doi:10.1002/prot.22667
  8. ↑ Mingot JM, Kostka S, Kraft R, Hartmann E, Gorlich D. Importin 13: a novel mediator of nuclear import and export. EMBO J. 2001 Jul 16;20(14):3685-94. PMID:11447110 doi:10.1093/emboj/20.14.3685
  9. ↑ Ploski JE, Shamsher MK, Radu A. Paired-type homeodomain transcription factors are imported into the nucleus by karyopherin 13. Mol Cell Biol. 2004 Jun;24(11):4824-34. PMID:15143176 doi:10.1128/MCB.24.11.4824-4834.2004
  10. ↑ Grunwald M, Bono F. Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation. EMBO J. 2010 Dec 7. PMID:21139563 doi:10.1038/emboj.2010.320

2xwu, resolution 2.80Å

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