Reactome | SUMOylation

SUMOylation

Stable Identifier

R-HSA-2990846

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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General

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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