Protein substrates can be modified with ubiquitin monomers on one or more acceptor sites, referred to as monoubiquitylation or multi-monoubiquitylation, respectively. Alternatively, ubiquitin monomers can be joined to each other via isopeptide bonds to form chains of varying lengths, linkages, and structures. Homotypic chains are linked uniformly through the same acceptor site of ubiquitin (e.g., K48-linked chains), whereas heterotypic chains contain multiple types of linkages and can be further classified as either mixed or branched. Mixed chains consist of ubiquitin subunits that are modified on only a single acceptor site. Branched chains contain at least one ubiquitin subunit that is simultaneously modified on multiple acceptor sites. Ubiquitins modified on one acceptor site are colored in blue or yellow; the branch point ubiquitin is colored in red; unmodified or “terminal” ubiquitins are colored gray.
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