ubiquitintagged

Ubiquitin-tagged refers to proteins that have been covalently modified by the small regulatory protein ubiquitin. This modification is typically accomplished through an enzymatic cascade involving ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), which attach ubiquitin to a substrate’s lysine residue via an isopeptide bond. The process can yield a single ubiquitin moiety (monoubiquitination) or polymeric chains (polyubiquitination) with different linkage types that influence cellular outcomes. The most common chains are linked through lysine 48 (K48), often signaling proteasomal degradation, and lysine 63 (K63), which is involved in signaling, endocytosis, and DNA repair; linear (M1) chains also participate in various signaling pathways.

Proteins can be ubiquitin-tagged temporarily; deubiquitinating enzymes (DUBs) remove ubiquitin, reversing the signal. Ubiquitin tagging affects protein fate: targeting to the 26S proteasome for degradation, altering subcellular localization, modulating activity, or mediating interactions with other proteins. Beyond quality control for misfolded proteins, ubiquitination participates in diverse processes such as cell cycle control, DNA damage response, and membrane trafficking.

Detection and study of ubiquitin-tagged proteins employ immunoblotting with anti-ubiquitin antibodies, mass spectrometry to identify modification sites and chain types, and enrichment techniques, including tandem ubiquitin binding entities. Abnormal ubiquitin tagging is implicated in diseases such as cancer, neurodegeneration, and inflammatory disorders.

The term ubiquitin-tagged is used broadly to describe any substrate carrying covalently attached ubiquitin, regardless of chain type or functional outcome.