3uin: Difference between revisions

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<StructureSection load='3uin' size='340' side='right'caption='[[3uin]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='3uin' size='340' side='right'caption='[[3uin]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3uin]] 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=3UIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UIN FirstGlance]. <br>
<table><tr><td colspan='2'>[[3uin]] 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=3UIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UIN 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;'>[[1z5s|1z5s]], [[3uio|3uio]], [[3uip|3uip]]</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]] 2.597&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBC9, UBCE9, UBE2I ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SMT3A, SMT3H2, SUMO2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), KIAA1835, RANGAP1, SD ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NUP358, RANBP2 ([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=3uin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uin OCA], [https://pdbe.org/3uin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uin RCSB], [https://www.ebi.ac.uk/pdbsum/3uin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uin 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=3uin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uin OCA], [https://pdbe.org/3uin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uin RCSB], [https://www.ebi.ac.uk/pdbsum/3uin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uin ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN]] Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:[https://omim.org/entry/608033 608033]]. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).<ref>PMID:19118815</ref> 
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN]] E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.<ref>PMID:11792325</ref> <ref>PMID:12032081</ref> <ref>PMID:15378033</ref> <ref>PMID:15931224</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/RAGP1_HUMAN RAGP1_HUMAN]] GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state. [[https://www.uniprot.org/uniprot/SUMO2_HUMAN SUMO2_HUMAN]] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins.<ref>PMID:9556629</ref> <ref>PMID:18538659</ref> <ref>PMID:18408734</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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The RanBP2 nucleoporin contains an internal repeat domain (IR1-M-IR2) that catalyzes E3 ligase activity and forms a stable complex with SUMO-modified RanGAP1 and UBC9 at the nuclear pore complex. RanBP2 exhibits specificity for SUMO1 as RanGAP1-SUMO1/UBC9 forms a more stable complex with RanBP2 in comparison to RanGAP1-SUMO2 that results in greater protection of RanGAP-SUMO1 from proteases. The IR1-M-IR2 SUMO E3 ligase activity also shows a similar preference for SUMO1. We utilized deletions and domain swap constructs in protease protection assays and auto-modification assays to define RanBP2 domains responsible for RanGAP1-SUMO1 protection and SUMO1-specific E3 ligase activity. Our data suggest that elements in both IR1 and IR2 exhibit specificity for SUMO1. IR1 protects RanGAP1-SUMO1/UBC9 and functions as the primary E3 ligase of RanBP2, while IR2 retains the ability to interact with SUMO1 to promote SUMO1-specific E3 ligase activity. To determine the structural basis for SUMO1 specificity, a hybrid IR1 construct and IR1 were used to determine three new structures for complexes containing UBC9 with RanGAP1-SUMO1/2. These structures show more extensive contacts between SUMO, UBC9 and RanBP2 in complexes containing SUMO1 in comparison to SUMO2 and suggest that differences in SUMO specificity may be achieved through these subtle conformational differences.
 
Determinants of SUMO1 specificity, E3 ligase and SUMO-RanGAP1 binding activities of the nucleoporin RanBP2.,Gareau JR, Reverter D, Lima CD J Biol Chem. 2011 Dec 22. PMID:22194619<ref>PMID:22194619</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3uin" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Gareau, J R]]
[[Category: Gareau JR]]
[[Category: Lima, C D]]
[[Category: Lima CD]]
[[Category: Reverter, D]]
[[Category: Reverter D]]
[[Category: E3]]
[[Category: Ligase]]
[[Category: Ligase-isomerase-protein binding complex]]
[[Category: Nuclear pore complex]]
[[Category: Ranbp2]]
[[Category: Sumo]]
[[Category: Ubc9]]

Latest revision as of 16:59, 14 March 2024

Complex between human RanGAP1-SUMO2, UBC9 and the IR1 domain from RanBP2Complex between human RanGAP1-SUMO2, UBC9 and the IR1 domain from RanBP2

Structural highlights

3uin is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.597Å
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]

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

3uin, resolution 2.60Å

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