2o25

Structural highlights

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]} [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.^{[9] [10] [11] [12] [13] [14] [15]}

Evolutionary Conservation

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

See Also

• SUMO conjugating enzyme Ubc9
• 3D structures of ubiquitin conjugating enzyme

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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
8. ↑ 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
9. ↑ 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
10. ↑ 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
11. ↑ 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
12. ↑ 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
13. ↑ 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
14. ↑ 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
15. ↑ 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