4mdk

Structural highlights

Function

UB2R1_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]}

See Also

• 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. ↑ Pati D, Meistrich ML, Plon SE. Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. Mol Cell Biol. 1999 Jul;19(7):5001-13. PMID:10373550
3. ↑ Charrasse S, Carena I, Brondani V, Klempnauer KH, Ferrari S. Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement of the Cdc34-SCF(p45Skp2) pathway. Oncogene. 2000 Jun 15;19(26):2986-95. PMID:10871850 doi:10.1038/sj.onc.1203618
4. ↑ Wu K, Chen A, Tan P, Pan ZQ. The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8 charged surface residues for efficient polyubiquitin chain assembly catalyzed by Cdc34. J Biol Chem. 2002 Jan 4;277(1):516-27. Epub 2001 Oct 23. PMID:11675391 doi:10.1074/jbc.M108008200
5. ↑ Semplici F, Meggio F, Pinna LA, Oliviero S. CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation. Oncogene. 2002 Jun 6;21(25):3978-87. PMID:12037680 doi:10.1038/sj.onc.1205574
6. ↑ Butz N, Ruetz S, Natt F, Hall J, Weiler J, Mestan J, Ducarre M, Grossenbacher R, Hauser P, Kempf D, Hofmann F. The human ubiquitin-conjugating enzyme Cdc34 controls cellular proliferation through regulation of p27Kip1 protein levels. Exp Cell Res. 2005 Feb 15;303(2):482-93. PMID:15652359 doi:10.1016/j.yexcr.2004.10.008
7. ↑ Sadowski M, Mawson A, Baker R, Sarcevic B. Cdc34 C-terminal tail phosphorylation regulates Skp1/cullin/F-box (SCF)-mediated ubiquitination and cell cycle progression. Biochem J. 2007 Aug 1;405(3):569-81. PMID:17461777 doi:10.1042/BJ20061812
8. ↑ Gazdoiu S, Yamoah K, Wu K, Pan ZQ. Human Cdc34 employs distinct sites to coordinate attachment of ubiquitin to a substrate and assembly of polyubiquitin chains. Mol Cell Biol. 2007 Oct;27(20):7041-52. Epub 2007 Aug 13. PMID:17698585 doi:10.1128/MCB.00812-07
9. ↑ Kleiger G, Saha A, Lewis S, Kuhlman B, Deshaies RJ. Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell. 2009 Nov 25;139(5):957-68. PMID:19945379 doi:S0092-8674(09)01356-7
10. ↑ Legesse-Miller A, Elemento O, Pfau SJ, Forman JJ, Tavazoie S, Coller HA. let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts. J Biol Chem. 2009 Mar 13;284(11):6605-9. doi: 10.1074/jbc.C900002200. Epub 2009, Jan 6. PMID:19126550 doi:10.1074/jbc.C900002200
11. ↑ 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
12. ↑ 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
13. ↑ Huang H, Ceccarelli DF, Orlicky S, St-Cyr DJ, Ziemba A, Garg P, Plamondon S, Auer M, Sidhu S, Marinier A, Kleiger G, Tyers M, Sicheri F. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin. Nat Chem Biol. 2013 Dec 15. doi: 10.1038/nchembio.1412. PMID:24316736 doi:http://dx.doi.org/10.1038/nchembio.1412