8a58

Structural highlights

Function

UBE2W_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in degradation of misfolded chaperone substrates by mediating monoubiquitination of STUB1/CHIP, leading to recruitment of ATXN3 to monoubiquitinated STUB1/CHIP, and restriction of the length of ubiquitin chain attached to STUB1/CHIP substrates by ATXN3. After UV irradiation, but not after mitomycin-C (MMC) treatment, acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Transfers ubiquitin in complex with RING/U-box type E3s that do not have active site cysteine residues to form thioester bonds with ubiquitin, and preferentially ubiquitinates the N-terminus of substrates, such as ATXN3, STUB1 and SUMO2.^{[1] [2] [3] [4] [5]}

References

1. ↑ Alpi AF, Pace PE, Babu MM, Patel KJ. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008 Dec 26;32(6):767-77. doi: 10.1016/j.molcel.2008.12.003. PMID:19111657 doi:http://dx.doi.org/10.1016/j.molcel.2008.12.003
2. ↑ 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
3. ↑ Zhang Y, Zhou X, Zhao L, Li C, Zhu H, Xu L, Shan L, Liao X, Guo Z, Huang P. UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2. Mol Cells. 2011 Feb;31(2):113-22. doi: 10.1007/s10059-011-0015-9. Epub 2010 Dec, 31. PMID:21229326 doi:http://dx.doi.org/10.1007/s10059-011-0015-9
4. ↑ 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
5. ↑ Scaglione KM, Basrur V, Ashraf NS, Konen JR, Elenitoba-Johnson KS, Todi SV, Paulson HL. The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. J Biol Chem. 2013 Jun 28;288(26):18784-8. doi: 10.1074/jbc.C113.477596. Epub 2013, May 21. PMID:23696636 doi:http://dx.doi.org/10.1074/jbc.C113.477596