SUMOylated

SUMOylated refers to a protein that has covalently attached a SUMO protein, a small ubiquitin-like modifier (UBL), via an isopeptide bond. SUMOylation is a reversible post-translational modification that regulates multiple aspects of a protein’s behavior, including activity, stability, interactions, and subcellular localization. In humans, SUMO-1 and SUMO-2/3 are the major isoforms; SUMO-2/3 can form polymeric chains, whereas SUMO-1 tends to function as a single modifier.

Attachment of SUMO proceeds through a three-step enzymatic cascade. A SUMO-activating E1 enzyme (SAE1/SAE2) activates SUMO, which is then transferred to the E2 conjugating enzyme Ubc9 (UBE2I). E3 ligases, such as members of the PIAS family or RanBP2, can enhance substrate specificity and efficiency. Substrates are typically modified on lysine residues within or near a consensus motif (ΨKxE), though many SUMOylation sites are non-consensus or context-dependent. SUMOylation can be mono- or polySUMOylation (the latter involving SUMO-2/3 chains). Reversal is catalyzed by SUMO-specific proteases (SENPs), which remove SUMO and restore unmodified proteins.

Biological consequences of SUMOylation are diverse. It can alter enzyme activity, change protein stability, influence subcellular localization, and reorganize protein interaction networks. SUMOylation plays key roles in transcriptional regulation, chromatin structure, DNA repair, cell cycle control, and nuclear transport. Its dynamics respond to stress, DNA damage, and signaling events, and there is extensive cross-talk with ubiquitination and other post-translational modifications.

Detection and study often use anti-SUMO antibodies, mass spectrometry to identify modification sites, or enrichment strategies with tagged SUMO. SUMOylation is evolutionarily conserved and widespread in eukaryotes; dysregulation has been linked to cancer, neurodegenerative diseases, and pathogen interactions with host SUMO pathways.

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