Ubiquitin conjugating enzyme

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spinqualitylabelsall models Structure of human ubiquitin conjugating enzyme E2 (green) complex with ubiquitin (deepskyblue) (PDB entry 3ptf) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Ubiquitin conjugating enzyme (Ubc) or E2 enzyme catalyzes the second step in the ubiquitination of a protein tagged to be degraded by the proteasome. Ubiquitin activating enzyme (E1) and ATP produce a C-terminal acyl adenylated ubiquitin molecule which binds to ubiquitin conjugating enzyme (E2) (Ubc) cysteine[1]. The Ubc then binds to ubiquitin ligase (E3) via a conserved binding region. E3 catalyzes the transfer of ubiquitin from the Ubc-ubiquitin complex to a lysine residue of the target protein. Ubc13 makes a catalytically active heterodimer with MMS2[2]. UBC2 is required for silencing in yeast[3]. UBC4 UBC5 mediate selective degradation of short-lived and abnormal proteins[4]. UBC6 participates in ER-associated protein degradation[5]. UBC7 or UBC13 is key in the process of tagging target proteins with Lys63-linked polyubiquitin[6]. For more details on Ubc13 see UBC13 MMS2. UBC8 is interferon-inducible[7]. UBC9 is required for sumoylation[8]. For more details on Ubc9 see SUMO conjugating enzyme Ubc9. UBC16 conjugates ubiquitin to its N-terminus and to that of the small ubiquitin-like modifier SUMO[9]. UBC D3 functions in the ubiquitination of the tumor suppressor p53. Medical importance UBC13 is required for metastatic spread and lung colonizationin breast cancer[10]. Structural highlights The active site of Ubc contains a cysteine residue. The [11].

3D Structures of ubiquitin conjugating enzyme

Updated on 02-October-2018

References

1. ↑ Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, Vidal M, Komander D, Serrano L, Lehner P, Sanderson CM. Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res. 2009 Oct;19(10):1905-11. Epub 2009 Jun 23. PMID:19549727 doi:http://dx.doi.org/gr.093963.109
2. ↑ Eddins MJ, Carlile CM, Gomez KM, Pickart CM, Wolberger C. Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nat Struct Mol Biol. 2006 Oct;13(10):915-20. Epub 2006 Sep 17. PMID:16980971 doi:10.1038/nsmb1148
3. ↑ Huang H, Kahana A, Gottschling DE, Prakash L, Liebman SW. The ubiquitin-conjugating enzyme Rad6 (Ubc2) is required for silencing in Saccharomyces cerevisiae. Mol Cell Biol. 1997 Nov;17(11):6693-9. PMID:9343433
4. ↑ Seufert W, Jentsch S. Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins. EMBO J. 1990 Feb;9(2):543-50. PMID:2154373
5. ↑ Lenk U, Yu H, Walter J, Gelman MS, Hartmann E, Kopito RR, Sommer T. A role for mammalian Ubc6 homologues in ER-associated protein degradation. J Cell Sci. 2002 Jul 15;115(Pt 14):3007-14. PMID:12082160
6. ↑ Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, Saitoh T, Yamamoto N, Sakurai H, Ishii KJ, Yamaoka S, Kawai T, Matsuura Y, Takeuchi O, Akira S. Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Nat Immunol. 2006 Sep;7(9):962-70. doi: 10.1038/ni1367. Epub 2006 Jul 23. PMID:16862162 doi:http://dx.doi.org/10.1038/ni1367
7. ↑ Kim KI, Giannakopoulos NV, Virgin HW, Zhang DE. Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation. Mol Cell Biol. 2004 Nov;24(21):9592-600. doi: 10.1128/MCB.24.21.9592-9600.2004. PMID:15485925 doi:http://dx.doi.org/10.1128/MCB.24.21.9592-9600.2004
8. ↑ Tahmasebi S, Ghorbani M, Savage P, Gocevski G, Yang XJ. The SUMO conjugating enzyme Ubc9 is required for inducing and maintaining stem cell pluripotency. Stem Cells. 2014 Apr;32(4):1012-20. doi: 10.1002/stem.1600. PMID:24706591 doi:http://dx.doi.org/10.1002/stem.1600
9. ↑ Tatham MH, Plechanovova A, Jaffray EG, Salmen H, Hay RT. Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini. Biochem J. 2013 Jul 1;453(1):137-45. doi: 10.1042/BJ20130244. PMID:23560854 doi:http://dx.doi.org/10.1042/BJ20130244
10. ↑ Wu X, Zhang W, Font-Burgada J, Palmer T, Hamil AS, Biswas SK, Poidinger M, Borcherding N, Xie Q, Ellies LG, Lytle NK, Wu LW, Fox RG, Yang J, Dowdy SF, Reya T, Karin M. Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade. Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13870-5. doi:, 10.1073/pnas.1414358111. Epub 2014 Sep 4. PMID:25189770 doi:http://dx.doi.org/10.1073/pnas.1414358111
11. ↑ Bosanac I, Phu L, Pan B, Zilberleyb I, Maurer B, Dixit VM, Hymowitz SG, Kirkpatrick DS. Modulation of K11-Linkage Formation by Variable Loop Residues within UbcH5A. J Mol Biol. 2011 May 6;408(3):420-31. Epub 2011 Mar 10. PMID:21396940 doi:10.1016/j.jmb.2011.03.011