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==The crystal structure of E2-25K and ubiquitin complex==
==The crystal structure of E2-25K and ubiquitin complex==
<StructureSection load='3k9p' size='340' side='right' caption='[[3k9p]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='3k9p' size='340' side='right'caption='[[3k9p]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3k9p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K9P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K9P FirstGlance]. <br>
<table><tr><td colspan='2'>[[3k9p]] 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=3K9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K9P FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k9o|3k9o]]</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]] 2.8&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2K, HIP2, LIG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3k9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k9p OCA], [https://pdbe.org/3k9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k9p RCSB], [https://www.ebi.ac.uk/pdbsum/3k9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k9p ProSAT]</span></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='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=3k9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k9p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k9p RCSB], [http://www.ebi.ac.uk/pdbsum/3k9p PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UBE2K_HUMAN UBE2K_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.<ref>PMID:8702625</ref> <ref>PMID:10634809</ref> <ref>PMID:10675012</ref> <ref>PMID:16714285</ref> <ref>PMID:16868077</ref> <ref>PMID:17873885</ref> <ref>PMID:20061386</ref> <ref>PMID:19906396</ref>
[https://www.uniprot.org/uniprot/UBE2K_HUMAN UBE2K_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.<ref>PMID:8702625</ref> <ref>PMID:10634809</ref> <ref>PMID:10675012</ref> <ref>PMID:16714285</ref> <ref>PMID:16868077</ref> <ref>PMID:17873885</ref> <ref>PMID:20061386</ref> <ref>PMID:19906396</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k9/3k9p_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k9/3k9p_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3k9p ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
E2-25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the frameshift mutant of ubiquitin B (UBB+1) and has been identified as a crucial factor regulating amyloid-beta neurotoxicity. To study the structural basis of the neurotoxicity mediated by the E2-25K/UBB+1 interaction, we determined the three-dimensional structures of UBB+1, E2 25K and the E2-25K/Ubiquitin and E2-25K/UBB+1 complexes. The structures revealed that ubiquitin or UBB+1 is bound to E2-25K via the enzyme's MGF motif and residues in alpha 9 of the enzyme. Polyubiquitylation assays, together with analyses of various E2-25K mutants, showed that disrupting UBB+1 binding markedly diminishes synthesis of neurotoxic UBB+1 anchored polyUb. These results suggest that the interaction between E2-25K and UBB+1 is critical for the synthesis and accumulation of UBB+1-anchored polyUb, which results in proteasomal inhibition and neuronal cell death.
Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity.,Ko S, Kang GB, Song SM, Lee JG, Shin DY, Yoon J, Sheng Y, Cheong C, Jeon YH, Jung YK, Arrowsmith CH, Avvakumov GV, Dhe-Paganon S, Yoo YJ, Eom SH, Lee W J Biol Chem. 2010 Sep 8. PMID:20826778<ref>PMID:20826778</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Ubiquitin|Ubiquitin]]
*[[Ubiquitin|Ubiquitin]]
*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ubiquitin--protein ligase]]
[[Category: Large Structures]]
[[Category: Eom, S H]]
[[Category: Eom SH]]
[[Category: Kang, G B]]
[[Category: Kang GB]]
[[Category: Ko, S]]
[[Category: Ko S]]
[[Category: Lee, W]]
[[Category: Lee W]]
[[Category: Song, S M]]
[[Category: Song SM]]
[[Category: Atp-binding]]
[[Category: Complex structure]]
[[Category: E2-25k]]
[[Category: Isopeptide bond]]
[[Category: Ligase]]
[[Category: Ligase-signaling protein complex]]
[[Category: Nucleotide-binding]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Ubiquitin]]
[[Category: Ubl conjugation pathway]]
Retrieved from "https://proteopedia.org/3k9p"