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3e46

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Revision as of 22:00, 2 December 2018

Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant

Structural highlights

3e46 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2bep, 2bf9, 1yla, 1jbb
Gene:	UBE2K, HIP2, LIG (HUMAN)
Activity:	Ubiquitin--protein ligase, with EC number 6.3.2.19
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the key protein in Huntington's disease) interacting protein and has been shown to play a role in mediating the toxicity of Abeta, the principal protein involved in Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating (UBC) domain which catalyzes the formation of a covalent bond between the C-terminal glycine of an ubiquitin molecule and the -amine of a lysine residue on the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to 1.9 and 2.2 A resolution, respectively. Examination of the structures revealed domain-domain interactions between the UBC and UBA domains which have not previously been reported.

Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2).,Wilson RC, Hughes RC, Flatt JW, Meehan EJ, Ng JD, Twigg PD Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 May 1;65(Pt, 5):440-4. Epub 2009 Apr 24. PMID:19407372^[9]

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

References

↑ Kalchman MA, Graham RK, Xia G, Koide HB, Hodgson JG, Graham KC, Goldberg YP, Gietz RD, Pickart CM, Hayden MR. Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme. J Biol Chem. 1996 Aug 9;271(32):19385-94. PMID:8702625
↑ Kikuchi J, Furukawa Y, Kubo N, Tokura A, Hayashi N, Nakamura M, Matsuda M, Sakurabayashi I. Induction of ubiquitin-conjugating enzyme by aggregated low density lipoprotein in human macrophages and its implications for atherosclerosis. Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):128-34. PMID:10634809
↑ Furukawa Y, Kubo N, Kikuchi J, Tokura A, Fujita N, Sakurabayashi I. Regulation of macrophage-specific gene expression by degenerated lipoproteins. Electrophoresis. 2000 Jan;21(2):338-46. PMID:10675012 doi:<338::AID-ELPS338>3.0.CO;2-9 http://dx.doi.org/10.1002/(SICI)1522-2683(20000101)21:2<338::AID-ELPS338>3.0.CO;2-9
↑ Yamada M, Ohnishi J, Ohkawara B, Iemura S, Satoh K, Hyodo-Miura J, Kawachi K, Natsume T, Shibuya H. NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF). J Biol Chem. 2006 Jul 28;281(30):20749-60. Epub 2006 May 19. PMID:16714285 doi:http://dx.doi.org/10.1074/jbc.M602089200
↑ Flierman D, Coleman CS, Pickart CM, Rapoport TA, Chau V. E2-25K mediates US11-triggered retro-translocation of MHC class I heavy chains in a permeabilized cell system. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11589-94. Epub 2006 Jul 25. PMID:16868077 doi:http://dx.doi.org/0605215103
↑ Christensen DE, Brzovic PS, Klevit RE. E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages. Nat Struct Mol Biol. 2007 Oct;14(10):941-8. Epub 2007 Sep 16. PMID:17873885 doi:http://dx.doi.org/10.1038/nsmb1295
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Oh KJ, Kalinina A, Bagchi S. Destabilization of Rb by human papillomavirus E7 is cell cycle dependent: E2-25K is involved in the proteolysis. Virology. 2010 Jan 5;396(1):118-24. doi: 10.1016/j.virol.2009.10.018. Epub 2009, Nov 10. PMID:19906396 doi:http://dx.doi.org/10.1016/j.virol.2009.10.018
↑ Wilson RC, Hughes RC, Flatt JW, Meehan EJ, Ng JD, Twigg PD. Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2). Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 May 1;65(Pt, 5):440-4. Epub 2009 Apr 24. PMID:19407372 doi:10.1107/S1744309109011117

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3e46"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant==
 <StructureSection load='3e46' size='340' side='right' caption='[[3e46]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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 HUMAN])</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=3e46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e46 OCA], [http://pdbe.org/3e46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e46 RCSB], [http://www.ebi.ac.uk/pdbsum/3e46 PDBsum]</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=3e46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e46 OCA], [http://pdbe.org/3e46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e46 RCSB], [http://www.ebi.ac.uk/pdbsum/3e46 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3e46 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e46_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e46_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 45: / Line 46: @@
 [[Category: Twigg, P D]]
 [[Category: Wilson, R C]]
+[[Category: Alternative splicing]]
+[[Category: Cytoplasm]]
 [[Category: E2-25k]]
 [[Category: Huntington interacting]]
 [[Category: Ligase]]
 [[Category: Ubiquitin-conjugating]]
+[[Category: Ubl conjugation]]
 [[Category: Ubl conjugation pathway]]

3e46

From Proteopedia

Revision as of 22:00, 2 December 2018

Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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