Reactome: A Curated Pathway Database

Processing and activation of SUMO (R-HSA-3215018.1)

Species Homo sapiens

Summation

The initial translation products of SUMO1, SUMO2, and SUMO3 are precursors that have extra amino acid residues at the C-terminus (reviewed in Wang and Dasso 2009, Wilkinson and Henley 2010, Hannoun et al. 2010, Gareau and Lima 2010, Hay 2007). SUMO1 has 4 extra residues, SUMO2 has 2 extra residues, and SUMO3 has 11 extra residues. Proteolytic cleavage by SUMO peptidases (SENPs) removes the propeptide and leaves diglycine residues at the C-terminus. Each SENP has distinct preferences for certain SUMOs. SENP1 has highest activity on SUMO1; SENP2 and SENP5 have highest activity on SUMO2 (Shen et al. 2006, Reverter and Lima 2006, Mikolajczyk et al. 2007). SENP1 and SENP2 are predominantly nucleoplasmic (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006) and SENP5 is predominantly nucleolar (Di Bacco et al. 2006, Gong and Yeh 2006), therefore the processing reactions are believed to occur in the nucleus. The processed SUMO is then activated by formation of a thioester bond with a cysteine residue of an E1 enzyme, UBA2 (SAE2) in a complex with SAE1. SUMO is then transferred from the E1 enzyme to an E2 enzyme, UBC9 (UBE2I).

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm
GO Biological Process protein sumoylation (0016925)
Literature References
pubMedId Title Journal Year
21102611 The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition Nat. Rev. Mol. Cell Biol. 2010
20674646 Post-translational modification by SUMO Toxicology 2010
20462400 Mechanisms, regulation and consequences of protein SUMOylation Biochem. J. 2010
19923268 SUMOylation and deSUMOylation at a glance J. Cell. Sci. 2009
14563852 Characterization of the localization and proteolytic activity of the SUMO-specific protease, SENP1 J. Biol. Chem. 2004
16253240 Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1 FEBS Lett. 2005
12192048 Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex Mol. Cell. Biol. 2002
11896061 Association of the human SUMO-1 protease SENP2 with the nuclear pore J. Biol. Chem. 2002
16738331 Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2 Mol. Cell. Biol. 2006
16738315 The SUMO-specific protease SENP5 is required for cell division Mol. Cell. Biol. 2006
17591783 Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs J. Biol. Chem. 2007
17099698 SUMO protease SENP1 induces isomerization of the scissile peptide bond Nat. Struct. Mol. Biol. 2006
17099700 Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates Nat. Struct. Mol. Biol. 2006
17768054 SUMO-specific proteases: a twist in the tail Trends Cell Biol. 2007