| Post Translational Modifications | Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30. Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones. Ubiquitin: (Microbial infection) Mono-ADP-ribosylated at Thr-66 by the C.violaceum CteC virulence factor. ADP-ribosylation causes the shutdown of polyubiquitin synthesis and disrupts the recognition and reversal of polyubiquitin. Small ribosomal subunit protein eS31: Monoubiquitinated at Lys-107 and Lys-113 by RNF25 in response to ribosome collisions (ribosome stalling): ubiquitination promotes subsequent activation of RNF14, leading to EEF1A1 ubiquitination and degradation and rescue of stalled ribosomes. Deubiquitination at Lys-113 by USP16 is required for maturation of the 40S ribosomal complex. |
| Function | Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair.Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation.Lys-29-linked is involved in proteotoxic stress response and cell cycle.Lys-33-linked is involved in kinase modification.Lys-48-linked is involved in protein degradation via the proteasome.Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Small ribosomal subunit protein eS31: Component of the 40S subunit of the ribosome. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. |
