This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3l1y

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of human UBC4 E2 conjugating enzyme

Structural highlights

3l1y is a 1 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 1.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UB2D2_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.^[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

Human E4B, also called UFD2a, is a U box-containing protein that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is thought to participate in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. The U box domain is an anchor site for E2 ubiquitin-conjugating enzymes, but little is known of the binding mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U box free and bound to UbcH5c and Ubc4 E2s. Whereas previously characterized U box domains are homodimeric, we show that E4B U box is a monomer stabilized by a network of hydrogen bonds identified from scalar coupling measurements. These structural studies, complemented by calorimetry- and NMR-based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B U box and provide a molecular basis to understand how the ubiquitylation machinery involving E4B assembles.

Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4.,Benirschke RC, Thompson JR, Nomine Y, Wasielewski E, Juranic N, Macura S, Hatakeyama S, Nakayama KI, Botuyan MV, Mer G Structure. 2010 Aug 11;18(8):955-65. PMID:20696396^[9]

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

References

↑ Gonen H, Bercovich B, Orian A, Carrano A, Takizawa C, Yamanaka K, Pagano M, Iwai K, Ciechanover A. Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha. J Biol Chem. 1999 May 21;274(21):14823-30. PMID:10329681
↑ Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem. 2004 Oct 1;279(40):42169-81. Epub 2004 Jul 26. PMID:15280377 doi:10.1074/jbc.M403362200
↑ Windheim M, Peggie M, Cohen P. Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology. Biochem J. 2008 Feb 1;409(3):723-9. PMID:18042044 doi:10.1042/BJ20071338
↑ Chiang MH, Chen LF, Chen H. Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation. Biol Reprod. 2008 Nov;79(5):914-20. doi: 10.1095/biolreprod.108.071407. Epub 2008, Aug 13. PMID:18703417 doi:10.1095/biolreprod.108.071407
↑ Grou CP, Carvalho AF, Pinto MP, Wiese S, Piechura H, Meyer HE, Warscheid B, Sa-Miranda C, Azevedo JE. Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor. J Biol Chem. 2008 May 23;283(21):14190-7. doi: 10.1074/jbc.M800402200. Epub 2008 , Mar 22. PMID:18359941 doi:10.1074/jbc.M800402200
↑ Zeng W, Xu M, Liu S, Sun L, Chen ZJ. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009 Oct 23;36(2):315-25. doi: 10.1016/j.molcel.2009.09.037. PMID:19854139 doi:10.1016/j.molcel.2009.09.037
↑ Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, Xu M, Chen ZJ. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell. 2010 Apr 16;141(2):315-30. doi: 10.1016/j.cell.2010.03.029. PMID:20403326 doi:10.1016/j.cell.2010.03.029
↑ 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
↑ Benirschke RC, Thompson JR, Nomine Y, Wasielewski E, Juranic N, Macura S, Hatakeyama S, Nakayama KI, Botuyan MV, Mer G. Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure. 2010 Aug 11;18(8):955-65. PMID:20696396 doi:10.1016/j.str.2010.04.017

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/3l1y"

Categories: Homo sapiens | Large Structures | Benirschke R | Mer G | Thompson JR

@@ Line 1: / Line 1: @@
 ==Crystal structure of human UBC4 E2 conjugating enzyme==
-<StructureSection load='3l1y' size='340' side='right' caption='[[3l1y]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='3l1y' size='340' side='right'caption='[[3l1y]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3l1y]] is a 1 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=3L1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L1Y FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3l1y]] is a 1 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=3L1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L1Y FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l1x|3l1x]], [[3l1z|3l1z]]</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]] 1.6&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2D2, UBC4, UBCH5B ([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=3l1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l1y OCA], [https://pdbe.org/3l1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l1y RCSB], [https://www.ebi.ac.uk/pdbsum/3l1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l1y 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=3l1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l1y OCA], [http://pdbe.org/3l1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l1y RCSB], [http://www.ebi.ac.uk/pdbsum/3l1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l1y ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref>
+[https://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 30: @@
 ==See Also==
-*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
+*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ubiquitin--protein ligase]]
+[[Category: Large Structures]]
-[[Category: Benirschke, R]]
+[[Category: Benirschke R]]
-[[Category: Mer, G]]
+[[Category: Mer G]]
-[[Category: Thompson, J R]]
+[[Category: Thompson JR]]
-[[Category: E2 conjugating enzyme]]
-[[Category: Ligase]]
-[[Category: Ubiquitin ligase]]
-[[Category: Ubl conjugation pathway]]

3l1y

From Proteopedia

Current revision

Crystal structure of human UBC4 E2 conjugating enzyme

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox