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).

References:

Koken MH, Reynolds P, Jaspers-Dekker I, Prakash L, Prakash S, Bootsma D, Hoeijmakers JH (1991) Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6. Proc Natl Acad Sci USA 88, 8865-9.

Kunapuli P, Somerville R, Still IH, Cowell JK (2003) ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins. Oncogene 22, 3417-23.

Nascimento RM, Otto PA, de Brouwer AP, Vianna-Morgante AM (2006) UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome. Am J Hum Genet 79, 549-55.

Sarcevic B, Mawson A, Baker RT, Sutherland RL (2002) Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation. EMBO J 21, 2009-18.

Ulrich HD, Jentsch S (2000) Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 19, 3388-97.

Ubiquigent Limited is a specialist developer and supplier of Drug Discovery Services, high quality Research Tools and Chemistry to the life science research community worldwide.

Ubiquigent’s scientific and business interests have a clear focus; namely the ubiquitin, ubiquitin-like, and integrated signalling systems.

The Company has established its scientific and business credentials with both academic researchers undertaking fundamental scientific discovery and pharmaceutical and biotechnology company scientists exploring the potential of ubiquitin cascade-focused drug discovery.

Ubiquigent benefits from high calibre backing including from private US investors, the UK Medical Research Council, and the University of Dundee. The Company’s headquarters and laboratory operations are based in the UK and are located in a state-of-the-art facility adjacent to the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee (both founded by Professor Sir Philip Cohen). In addition to Ubiquigent’s own facilities and capabilities, such proximity provides ready access to a huge range of additional scientific expertise (1,000+ life-science researchers on site), technological competencies, and assay and analytical platforms.

Ubiquigent staff have a wealth of scientific experience, technological competencies and commercial expertise, gained from within academia, the life science research reagents and services sector, and the pharmaceutical industry, that enables the Company to offer a level of understanding and service to its customers and clients worldwide that few companies may match.