Table 1.
Functions of various Ub-linkages and the cellular processes involved.
| Type of Ub-linkages | Target | Recognizing molecules | Functions |
|---|---|---|---|
| Monoubiquitination or multi-monoubiquitination | Normally folded proteins | Ub + Ub-binding receptors | Protein interactions, localization, trafficking, activity modulation, DNA repair, endocytosis, transcription, proteasomal degradation |
| K63 poly-Ub chains | Normally folded proteins | Ub + Ub-binding receptors + accessory proteins | NFKB1 signaling, DNA repair, trafficking, endocytosis |
| Branched Ub-chains | Normally folded proteins | Ub + Ub-binding receptors + accessory proteins | APC/cyclosome-mediated proteasomal degradation |
| K11, K48 poly-Ub chains | Normally folded proteins | Ub + Ub-binding receptors | Proteasomal degradation |
| K48 (other linkages?) poly-Ub chains | Misfolded protein aggregates | Ub + Ub-binding receptors | Autophagic degradation |
| K63 poly-Ub chains | Misfolded protein aggregates | Ub + Ub-binding receptors + LC3 + chaperones | Autophagic degradation |
| (other linkages?) | |||
| K63 | Damaged mitochondria | Ub + Ub-binding receptors + LC3 + chaperones | Autophagic degradation including mitophagy, pexophagy, xenophagy, reticulophagy? ribophagy? lipophagy? |
| K6 (?) poly-Ub chains | |||
| K27, K29, K33, Lys6 (?) poly-Ub chains | Normally folded proteins | Ub + Ub-binding receptors + accessary protein | Non-proteolytic processes |
| Met1-linear chain | Normally folded proteins | Ub + Ub-binding receptors + accessory protein | Signaling |
The information provided by specific Ub-linkages “Ub-codes” are interpreted by specialized proteins consisting of UBDs and sometimes involve accessory proteins. The receptors having UBDs recognize the length and type of Ub chains on protein substrates and couple ubiquitinated cargos to subsequent downstream events. Majorly, monoubiquitination or multi-monoubiquitination plays role in protein-protein interaction, localization, endocytosis, proteasomal degradation, DNA repair, transcription, regulation of protein activity, and link ubiquitinated target to autophagy. K48 and K11-linked Ub chains specify proteasomal-mediated degradation of short-lived and misfolded proteins. Conjugation of K48 and K63-linked Ub chains to the misfolded proteins targets them for proteasome or autophagy-mediated degradation. K63-linked Ub chain also directs the autophagic degradation of damaged cellular materials, including mitochondria, and targets intracellular cytosolic pathogens to autophagy. K63-linked chains are involved in assembling many signaling cascades, including NFKB signaling, DNA repair, trafficking, and endocytosis. Met1-linked linear chains target intracellular bacteria and act as assembly signals for downstream NFKB signaling. Compared to atypical Ub linkages, including K6, K27, K29, K33, and branched Ub, the functions of K48 and K63 linkages are known. The diverse functions of atypical Ub linkages and branched Ub are emerging now.