This has been demonstrated by gene ablation studies in yeast and C. elegans where UBA1 is the only ubiquitin E1 (McGrath et al., 1991; Kulkarni and Smith, 2008), but also in various human cancer cell lines (Xu et al., 2010) where UBA6 is apparently not able to compensate for the loss of UBA1. The gene discussed is UBA1; the disease is cancer.