Ubiquitin chains occur when ubiquitin proteins are linked by the carboxy terminus of one ubiquitin to one of lysine residues (K6, K11, K27, K29, K33, K48, and K63) or the N-terminal methionine residue (M1) on the other ubiquitin. Ubiquitin chains that comprise only a single linkage type are called homotypic. In contrast, heterotypic chains contain mixed linkages within the same polymer.
In homotypic chains, M1 chains have been associated with NF-κB signaling, K6 with DNA damage response, K11 with endoplasmic reticulum associated degradation (ERAD), proteasomal degradation, and cell cycle control, K27 with nuclear translocation and innate immunity, K29 with Wnt signaling, K33 with AMPK-related kinase signaling and protein trafficking, and K63 with DNA repair, NF-κB signaling, protein trafficking and activation of protein kinases. K48 ubiquitin chains attract the 26 S proteasome complex, and results in degradation of the substrate protein.