Activates ubiquitin by first adenylating with ATP its C-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Catalyzes the ISGylation of influenza A virus NS1 protein. Protein modification; protein ubiquitination. Monomer (By similarity). Binds and is involved in the conjugation of G1P2/ISG15. Expressed in a variety of normal and tumor cell types, but is reduced in lung cancer cell lines. ISGylated. There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site. Belongs to the ubiquitin-activating E1 family.