Background
The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including regulated and targeted proteasomal degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). UBE2V2 is a member of the E2 conjugating enzyme family and cloning of the human gene was first described by Fritsche et al. (1997). UBE2V2 shares 90% sequence identity with UBE2V1 in its C-terminal domain (Sancho et al., 1998). The UEV protein Mms2 (yeast homologue of human UBE2V2) forms a heterodimer with yeast Ubc13 (UBE2N) which is recruited to chromatin by the RING finger proteins RAD5 and RAD18 in the RAD6 dependent post-replicative DNA repair pathway (Hofmann and Pickart 1999). These proteins also play a central role in the assembly of K63-linked polyubiquitin chains (Ulrich and Jentsch 2000; Xiao et al., 1998). UEV/Ubc complexes have been implicated in the assembly of Lys63-linked polyubiquitin chains that act as a novel signal in post-replicative DNA repair and IκBα kinase activation. Recent crystal structure analysis provides direct evidence that the Mms2/Ubc13 heterodimer is necessary for DNA repair (Moraes et al., 2001).
References
Fritsche, J., M. Rehli, et al. (1997). Molecular cloning of a 1alpha,25-dihydroxyvitamin D3-inducible transcript (DDVit 1) in human blood monocytes. Biochem Biophys Res Commun 235(2): 407-12.
Hofmann RM, Pickart CM (1999). Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-53.
Moraes, T. F., R. A. Edwards, et al. (2001). Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13. Nat Struct Biol 8(8): 669-73.
Sancho, E., M. R. Vila, et al. (1998). Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Mol Cell Biol 18(1): 576-89.
Ulrich, H. D. and S. Jentsch (2000). Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 19(13): 3388-97.
Xiao, W., S. L. Lin, et al. (1998). The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family. Nucleic Acids Res 26(17): 3908-14.