The reaction involved in the attachment of ubiquitin to a protein. In the first part the carboxyl group of ubiquitin in coupled to E1 by a thioether linkage in a reaction driven by ATP hydrolysis. The activated ubiquitin is subsequently transferred to a sulphydryl group of E2 and then in a reaction catalysed by E3 to the e-amino group of a Lys residue on a condemned protein, thereby flagging the protein for proteolytic degradation by the 26S proteasome