The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the 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). UBE2A is a member of the E2 conjugating enzyme family and cloning of the human gene was first described by Koken et al. (1991). UBE2A shares 70% identity with its yeast homologue but lacks the acidic C-terminal domain. The ring finger proteins RAD5 and RAD18 interact with UBE2A and other members of the RAD6 pathway (Ulrich and Jentsch, 2000). Phosphorylation of UBE2A by CDK1 and 2 increases its activity during the G2/M phase of the cell cycle (Sarcevic et al., 2002). UBE2A is required for post-replicative DNA damage repair in eukaryotic cells and it is thought binding to ZNF198 may be involved in this process (Kunapuli et al., 2003). A nonsense mutation resulting in the loss of a 25 amino acid region in the C-terminal domain of UBE2A has been identified as a cause of a novel X-linked mental retardation (XLMR) syndrome (Nascimento et al., 2006).
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