Disease relevance of UBE2A

• UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome [1].

High impact information on UBE2A

• Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation [2].
• In vivo, hHR6A phosphorylation peaks during the G2/M phase of cell cycle transition, with a concomitant increase in histone H2B ubiquitylation [2].
• Genetic complementation studies in S.cerevisiae demonstrated that hHR6A Ser120 is critical for cellular proliferation [2].
• Mutation of Ser120 to threonine or alanine abolished hHR6A activity, while mutation to aspartate to mimic phosphorylated serine increased hHR6A activity 3-fold [2].
• We have cloned the two human RAD6 homologs, designated HHR6A and HHR6B [3].
• UBE2A is the E2 ubiquitin conjugating enzyme that functions together with RNF20 and RNF40 to catalyze histone H2B monoubiquitination [4].
• UBE2A cooperates with RAD18 to ubiquitinate PCNA in response to DNA damage [5].

Biological context of UBE2A

• The deduced amino acid sequence is 77% identical to the human E2, HHR6A and HHR6B [6].
• HR6B and its nearly identical homolog HR6A are multiple function proteins, with ubiquitin-conjugating activity and essential roles in post-replication DNA repair [7].

Other interactions of UBE2A

• Two closely related human homologs of yeast Rad6 have been identified as HHR6A and HHR6B [8].
• Thus, through interaction and complex formation with HHR6A and HHR6B, RAD18 protein may play an important role in lesion bypass mechanisms in humans [8].

References