Ubiquitin-activating Enzyme E1

Supporting information

Ubiquitin-activating enzyme E1 catalyzes the first stage of the multistep enzymatic cascade of ubiquitination. The E1 enzyme binds to a ubiquitin molecule which is subsequently transferred to E2 enzymes, E3 enzymes, and then finally the target protein. Unlike the remainder of the ubiquitin-proteasome system, this enzymatic step is dependent on ATP.

There are currently two recognized E1 enzymes that catalyze the first stage of ubiquitination - UBA1 and UBA6 - with a further six related E1 enzymes identified that are involved in additional, ubiquitination-like processes such as SUMOylation and Neddylation. E1 enzymes are crucial for establishing specificity within the UPS, since they correctly match a ubiquitin molecule to an appropriate cognate E2 enzyme.

Studies on cells with mutations in UBA1 demonstrated the influence of E1 enzymes on cellular processes: UBA1 mutants displayed decreased cell proliferation and ubiquitin conjugation, and cell cycle arrest at the G2/M phase. Endocytosis of growth hormone receptors was also shown to be abolished in E1 mutant cells, whilst conditional yeast E1 mutants display a defect in the Rad23-mediated delivery of target substrates to the proteasome, demonstrating the importance of E1 in a wide array of cellular processes.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Ubiquitin-like modifier activating enzyme 1 (UBA1) Human UBA1 NM_003334 P22314
Mouse Uba1 NM_001276316 Q02053
Rat Uba1 NM_001014080 Q5U300
Ubiquitin-like modifier activating enzyme 6 (UBA6) Human UBA6 NM_018227 A0AVT1
Mouse Uba6 NM_172712 Q8C7R4
Rat Uba6 NM_001107213 NP_001100683

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