Ubiquitin

Ubiquitin is a small protein attached to other proteins in cellular sorting and regulation, including targeting many substrates to a proteasome.

Ubiquitination covalently attaches ubiquitin to a substrate, usually through successive action of a ubiquitin-activating enzyme, ubiquitin-conjugating enzyme and ubiquitin ligase. The modification can change degradation, localization or signalling; attachment alone does not specify which outcome occurs.

A ubiquitin ligase, or E3, promotes transfer of ubiquitin to a selected substrate within the ubiquitination system. Many E3s provide substrate recognition, while the detailed chemistry differs between E3 families. A ubiquitin-conjugating enzyme supplies activated ubiquitin. The resulting modification can signal protein degradation or other fates depending on substrate, linkage and context, so ubiquitination is not synonymous with immediate destruction. ^[ref]

A substrate-recognition protein in an iron-sensitive ubiquitin-ligase pathway controlling IRP2. Its stability depends on iron and oxygen conditions.^[ref]

A substrate-recognition component of a ubiquitin ligase that recognizes phosphorylated substrates, including Sic1.

As part of an SCF-type assembly, it links a substrate’s phosphorylation state to ubiquitin-dependent turnover. The recognition step explains why adding phosphate can change protein lifetime without directly destroying the modified protein. ^[ref]

A ubiquitin-conjugating enzyme, or E2, accepts activated ubiquitin from a ubiquitin-activating enzyme onto a catalytic cysteine. It then works with a ubiquitin ligase to transfer ubiquitin onward. Pairing between E2 and E3 helps determine which modification is assembled. This division of labour separates initial energy-dependent activation from later substrate selection and transfer. ^[ref]

A ubiquitin-activating enzyme, or E1, uses ATP to activate ubiquitin and forms a covalent intermediate through a catalytic cysteine. Ubiquitin is then passed to a ubiquitin-conjugating enzyme. ATP consumption occurs at this activation stage, while the downstream relay handles targeting and transfer. This creates a chemically activated donor for controlled covalent protein modification. ^[ref]

A deubiquitinating enzyme cleaves ubiquitin from a substrate or edits ubiquitin chains. Removing a modification can rescue a substrate from recognition, recycle ubiquitin during degradation, or change a signalling outcome.