4s3o

Structural highlights

Function

UB2D3_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]}

See Also

• Polycomb complex proteins 3D structures
• Ubiquitin protein ligase 3D structures
• 3D structures of ubiquitin conjugating enzyme

References

1. ↑ 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
2. ↑ Murata S, Minami Y, Minami M, Chiba T, Tanaka K. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001 Dec;2(12):1133-8. Epub 2001 Nov 21. PMID:11743028 doi:http://dx.doi.org/10.1093/embo-reports/kve246
3. ↑ Yogosawa S, Miyauchi Y, Honda R, Tanaka H, Yasuda H. Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. Biochem Biophys Res Commun. 2003 Mar 21;302(4):869-72. PMID:12646252
4. ↑ Rajendra R, Malegaonkar D, Pungaliya P, Marshall H, Rasheed Z, Brownell J, Liu LF, Lutzker S, Saleem A, Rubin EH. Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J Biol Chem. 2004 Aug 27;279(35):36440-4. Epub 2004 Jul 9. PMID:15247280 doi:http://dx.doi.org/10.1074/jbc.C400300200
5. ↑ 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
6. ↑ Huang J, Huang Q, Zhou X, Shen MM, Yen A, Yu SX, Dong G, Qu K, Huang P, Anderson EM, Daniel-Issakani S, Buller RM, Payan DG, Lu HH. The poxvirus p28 virulence factor is an E3 ubiquitin ligase. J Biol Chem. 2004 Dec 24;279(52):54110-6. Epub 2004 Oct 20. PMID:15496420 doi:http://dx.doi.org/10.1074/jbc.M410583200
7. ↑ Polanowska J, Martin JS, Garcia-Muse T, Petalcorin MI, Boulton SJ. A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites. EMBO J. 2006 May 17;25(10):2178-88. Epub 2006 Apr 20. PMID:16628214 doi:http://dx.doi.org/10.1038/sj.emboj.7601102
8. ↑ Ohbayashi N, Okada K, Kawakami S, Togi S, Sato N, Ikeda O, Kamitani S, Muromoto R, Sekine Y, Kawai T, Akira S, Matsuda T. Physical and functional interactions between ZIP kinase and UbcH5. Biochem Biophys Res Commun. 2008 Aug 8;372(4):708-12. doi:, 10.1016/j.bbrc.2008.05.113. Epub 2008 Jun 2. PMID:18515077 doi:10.1016/j.bbrc.2008.05.113
9. ↑ Zhang S, Chea J, Meng X, Zhou Y, Lee EY, Lee MY. PCNA is ubiquitinated by RNF8. Cell Cycle. 2008 Nov 1;7(21):3399-404. PMID:18948756
10. ↑ Umebayashi K, Stenmark H, Yoshimori T. Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation. Mol Biol Cell. 2008 Aug;19(8):3454-62. doi: 10.1091/mbc.E07-10-0988. Epub 2008, May 28. PMID:18508924 doi:http://dx.doi.org/10.1091/mbc.E07-10-0988
11. ↑ Kubori T, Hyakutake A, Nagai H. Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol. 2008 Mar;67(6):1307-19. doi: 10.1111/j.1365-2958.2008.06124.x., Epub 2008 Feb 13. PMID:18284575 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06124.x
12. ↑ 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
13. ↑ Wu K, Kovacev J, Pan ZQ. Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrate. Mol Cell. 2010 Mar 26;37(6):784-96. doi: 10.1016/j.molcel.2010.02.025. PMID:20347421 doi:10.1016/j.molcel.2010.02.025
14. ↑ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011 Jun 2;474(7349):105-8. doi: 10.1038/nature09966. Epub 2011 May 1. PMID:21532592 doi:10.1038/nature09966
15. ↑ Taherbhoy AM, Huang OW, Cochran AG. BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase. Nat Commun. 2015 Jul 7;6:7621. doi: 10.1038/ncomms8621. PMID:26151332 doi:http://dx.doi.org/10.1038/ncomms8621