| Structural highlights
Function
[UBE2B_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA. Associates to the E3 ligase RAD18 to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. May be involved in neurite outgrowth.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The human ubiquitin-conjugating enzyme Rad6 (E2), with ubiquitin ligase enzyme Rad18 (RING E3), monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Here, we determine the structure of the homodimeric Rad18 RING domains by X-ray crystallography and classify it to RING-RING dimers that dimerize through helices adjacent to the RING domains and through the canonical RING domains. Using NMR spectroscopy and site-directed mutagenesis, we demonstrate that the Rad6b binding site, for the Rad18 RING domain, strongly resembles that of other E2/E3 RING/U-box complexes. We show that the homodimeric Rad18 RING domain can recruit two Rad6b E2 enzymes, whereas the full-length Rad18 homodimer binds only to a single Rad6b molecule. Such asymmetry is a common feature of RING-RING heterodimers and has been observed for the CHIP U-box homodimer. We propose that asymmetry may be a common feature of dimeric RING E3 ligases.
Symmetry and Asymmetry of the RING-RING Dimer of Rad18.,Huang A, Hibbert RG, de Jong RN, Das D, Sixma TK, Boelens R J Mol Biol. 2011 Jul 15;410(3):424-35. Epub 2011 Apr 27. PMID:21549715[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Koken MH, Reynolds P, Jaspers-Dekker I, Prakash L, Prakash S, Bootsma D, Hoeijmakers JH. Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8865-9. PMID:1717990
- ↑ Kim J, Hake SB, Roeder RG. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol Cell. 2005 Dec 9;20(5):759-70. PMID:16337599 doi:https://dx.doi.org/10.1016/j.molcel.2005.11.012
- ↑ Motegi A, Sood R, Moinova H, Markowitz SD, Liu PP, Myung K. Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. J Cell Biol. 2006 Dec 4;175(5):703-8. Epub 2006 Nov 27. PMID:17130289 doi:10.1083/jcb.200606145
- ↑ Unk I, Hajdu I, Fatyol K, Szakal B, Blastyak A, Bermudez V, Hurwitz J, Prakash L, Prakash S, Haracska L. Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18107-12. Epub 2006 Nov 15. PMID:17108083 doi:0608595103
- ↑ 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
- ↑ Huang A, Hibbert RG, de Jong RN, Das D, Sixma TK, Boelens R. Symmetry and Asymmetry of the RING-RING Dimer of Rad18. J Mol Biol. 2011 Jul 15;410(3):424-35. Epub 2011 Apr 27. PMID:21549715 doi:10.1016/j.jmb.2011.04.051
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