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The SUMO pathway is a post-translational modification system where Small Ubiquitin-like Modifier proteins (approximately 100 amino acids, 12 kDa) are covalently and reversibly attached to target proteins through an isopeptide bond. The modification occurs through an enzymatic cascade involving E1 activating enzymes (SAE1/SAE2 heterodimer), E2 conjugating enzyme (Ubc9), and E3 ligases. SUMO shares structural similarity with ubiquitin despite having less than 20% sequence identity. The pathway regulates numerous cellular processes including protein localization, stability, activity, and protein-protein interactions through SUMO-interacting motifs (SIMs). SUMOylation is reversible through SUMO-specific proteases (SENPs). The pathway affects chromatin structure, transcriptional regulation (generally associated with repression), DNA repair, nuclear transport, and formation of nuclear bodies like PML bodies and Polycomb bodies. Target proteins are typically modified at lysine residues within a consensus sequence (ΨKXE/D). The modification is dynamic, with typically only a small fraction of any given protein being SUMOylated at any time.
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