UBE2D3 explained

Ubiquitin-conjugating enzyme E2 D3 is a protein that in humans is encoded by the UBE2D3 gene.^{[1] [2]}

Function

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme functions in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. Multiple spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined.^[2]

Interactions

UBE2D3 has been shown to interact with NEDD4.^{[3] [4]}

Further reading

• Scheffner M, Huibregtse JM, Howley PM . Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53 . Proceedings of the National Academy of Sciences of the United States of America . 91 . 19 . 8797–801 . Sep 1994 . 8090726 . 44693 . 10.1073/pnas.91.19.8797 . 1994PNAS...91.8797S . free .
• Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM . DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 . The Journal of Biological Chemistry . 273 . 10 . 5858–68 . Mar 1998 . 9488723 . 10.1074/jbc.273.10.5858 . free .
• Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, Kuwano A, Matsuda I, Endo F, Saya H, Nakao M . Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes . Genes to Cells . 3 . 11 . 751–63 . Nov 1998 . 9990509 . 10.1046/j.1365-2443.1998.00227.x . 1653536 .
• 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 . The Journal of Biological Chemistry . 274 . 21 . 14823–30 . May 1999 . 10329681 . 10.1074/jbc.274.21.14823 . free .
• Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E, Israël A, Mercurio F, Iwai K, Schwartz AL, Ciechanover A . SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase . The EMBO Journal . 19 . 11 . 2580–91 . Jun 2000 . 10835356 . 212749 . 10.1093/emboj/19.11.2580 .
• Coleman CS, Pegg AE . Polyamine analogues inhibit the ubiquitination of spermidine/spermine N1-acetyltransferase and prevent its targeting to the proteasome for degradation . The Biochemical Journal . 358 . Pt 1 . 137–45 . Aug 2001 . 11485561 . 1222041 . 10.1042/0264-6021:3580137 .
• Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ . Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase . The Journal of Biological Chemistry . 277 . 24 . 22085–92 . Jun 2002 . 11927591 . 10.1074/jbc.M201252200 . free .
• Obin M, Lee BY, Meinke G, Bohm A, Lee RH, Gaudet R, Hopp JA, Arshavsky VY, Willardson BM, Taylor A . Ubiquitylation of the transducin betagamma subunit complex. Regulation by phosducin . The Journal of Biological Chemistry . 277 . 46 . 44566–75 . Nov 2002 . 12215439 . 10.1074/jbc.M205308200 . free .
• Takeyama K, Aguiar RC, Gu L, He C, Freeman GJ, Kutok JL, Aster JC, Shipp MA . The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity . The Journal of Biological Chemistry . 278 . 24 . 21930–7 . Jun 2003 . 12670957 . 10.1074/jbc.M301157200 . free .
• Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R . Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex . Proceedings of the National Academy of Sciences of the United States of America . 100 . 10 . 5646–51 . May 2003 . 12732733 . 156255 . 10.1073/pnas.0836054100 . 2003PNAS..100.5646B . free .
• Tang ED, Wang CY, Xiong Y, Guan KL . A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha . The Journal of Biological Chemistry . 278 . 39 . 37297–305 . Sep 2003 . 12867425 . 10.1074/jbc.M303389200 . free .
• Subramaniam V, Li H, Wong M, Kitching R, Attisano L, Wrana J, Zubovits J, Burger AM, Seth A . The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase . British Journal of Cancer . 89 . 8 . 1538–44 . Oct 2003 . 14562029 . 2394340 . 10.1038/sj.bjc.6601301 .
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–67 . Jan 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
• 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 . The Journal of Biological Chemistry . 279 . 40 . 42169–81 . Oct 2004 . 15280377 . 10.1074/jbc.M403362200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . Jan 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .

Notes and References

1. Jensen JP, Bates PW, Yang M, Vierstra RD, Weissman AM . Identification of a family of closely related human ubiquitin conjugating enzymes . The Journal of Biological Chemistry . 270 . 51 . 30408–14 . Dec 1995 . 8530467 . 10.1074/jbc.270.51.30408 . free .
2. Web site: Entrez Gene: UBE2D3 ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast).
3. Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, Kuwano A, Matsuda I, Endo F, Saya H, Nakao M . Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes . Genes to Cells . 3 . 11 . 751–63 . Nov 1998 . 9990509 . 10.1046/j.1365-2443.1998.00227.x . 1653536 .
4. Wang X, Shi Y, Wang J, Huang G, Jiang X . Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation . The Biochemical Journal . 414 . 2 . 221–9 . Sep 2008 . 18498243 . 10.1042/BJ20080674 .