Stable Identifier
Homo sapiens
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Small Ubiquitin-like MOdifiers (SUMOs) are a family of 3 proteins (SUMO1,2,3) that are reversibly conjugated to lysine residues of target proteins via a glycine-lysine isopeptide bond (reviewed in Hay 2013, Hannoun et al. 2010, Gareau and Lima 2010, Wilkinson and Henley 2010, Wang and Dasso 2009). Proteomic methods have yielded estimates of hundreds of target proteins. Targets are mostly located in the nucleus and therefore SUMOylation disproportionately affects gene expression.
SUMOs are initially translated as proproteins possessing extra amino acid residues at the C-terminus which are removed by the SUMO processing endoproteases SENP1,2,5 (Hay 2007). Different SENPs have significantly different efficiencies with different SUMOs. The processing exposes a glycine residue at the C-terminus that is activated by ATP-dependent thiolation at cysteine-173 of UBA2 in a complex with SAE1, the E1 complex. The SUMO is transferred from E1 to cysteine-93 of a single E2 enzyme, UBC9 (UBE2I). UBC9 with or, in some cases, without an E3 ligase conjugates the glycine C-terminus of SUMO to an epsilon amino group of a lysine residue on the target protein. SUMO2 and SUMO3 may then be further polymerized, forming chains. SUMO1 is unable to form polymers.
Conjugated SUMO can act as a biinding site for proteins possessing SUMO interaction motifs (SIMs) and can also directly affect the formation of complexes between the target protein and other proteins.
Conjugated SUMOs are removed by cleavage of the isopeptide bond by processing enzymes SENP1,2,3,5. The processing enzymes SENP6 and SENP7 edit chains of SUMO2 and SUMO3.
Literature References
PubMed ID Title Journal Year
17768054 SUMO-specific proteases: a twist in the tail

Hay, RT

Trends Cell Biol. 2007
20674646 Post-translational modification by SUMO

Hay, RT, Hannoun, Z, Jaffray, E, Greenhough, S, Hay, DC

Toxicology 2010
19923268 SUMOylation and deSUMOylation at a glance

Dasso, M, Wang, Y

J. Cell. Sci. 2009
20462400 Mechanisms, regulation and consequences of protein SUMOylation

Henley, JM, Wilkinson, KA

Biochem. J. 2010
23514139 Decoding the SUMO signal

Hay, RT

Biochem. Soc. Trans. 2013
21102611 The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition

Gareau, JR, Lima, CD

Nat. Rev. Mol. Cell Biol. 2010
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