Properties of ubiquitin-activating enzymes: UBA1 and UBA6 (McGrath et al., 1991; Groettrup et al., 2008; Kulkarni and Smith, 2008; Clague et al., 2015; Hyer et al., 2018)
| Enzyme | UBA1 | UBA6 |
|---|---|---|
| Identitya | 100% | 40% |
| Molecular mass | 118 kDa | 118 kDa |
| UBL | Ubiquitin | Ubiquitin; FAT10 |
| Contribution to cellular ubiquitylation | >99% | <1% |
| E2 enzymesc | Ubiquitin E2s except for USE1 | Ubiquitin: Few E2s and USE1 is UBA6-specific |
| FAT10: Unknown | ||
| Preferential activity toward ubiquitin under basal conditions; cytokines (e.g., IFN-γ) increase activity toward FAT10 | ||
| Knockout phenotyped | Lethality in Caenorhabditis elegans and yeast | Embryonic lethality in mice |
| Expressione | Constitutively expressed in relatively large amounts in all tissues | Expressed in low amounts (compared with UBA1) in all tissues, with specifically higher expression in the testis |
| Ubiquitin charging in proliferating cells | Fully charged with ubiquitin | 50% charged |
↵a Percent amino acid identity relative to UBA1.
b FAT10 was reported to serve as a post-translational modification to direct proteins to proteasomal degradation.
↵c Nine E2s were reported to be charged equally by UBA1 and UBA6.
↵d Embryonic lethality of knockout phenotypes may indicate that UBA1 and UBA6 are not merely redundant versions of each other and that each of them is required for distinct essential biologic functions.
↵e UBA1 is ranked among the top 2% of abundant proteins in HeLa cells (>3 × 106 copies per cell), and the relative UBA1:UBA6 abundance ratio is approximately 10:1.