Reactome | SUMO E3 ligases SUMOylate target proteins

SUMO E3 ligases SUMOylate target proteins

Stable Identifier

R-HSA-3108232

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

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SUMO E3 ligases SUMOylate target proteins

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SUMO proteins are conjugated to lysine residues of target proteins via an isopeptide bond with the C-terminal glycine of SUMO (reviewed in Zhao 2007, Gareau and Lima 2010, Hannoun et al. 2010, Citro and Chiocca 2013, Yang and Chiang 2013). Proteomic analyses indicate that SUMO is conjugated to hundreds of proteins and most targets of SUMOylation are nuclear (Vertegal et al. 2006, Bruderer et al. 2011, Tatham et al. 2011, Da Silva et al. 2012, Becker et al. 2013). Within the nucleus SUMOylation targets include transcription factors (TFs), transcription cofactors (TCs), intracellular (nuclear) receptors, RNA binding proteins, RNA splicing proteins, polyadenylation proteins, chromatin organization proteins, DNA replication proteins, DNA methylation proteins, DNA damage response and repair proteins, immune response proteins, SUMOylation proteins, and ubiquitinylation proteins. Mitochondrial fission proteins are SUMOylated at the mitochondrial outer membrane.
UBE2I (UBC9), the E2 activating enzyme of the SUMO pathway, is itself also a SUMO E3 ligase. Most SUMOylation reactions will proceed with only the substrate protein and the UBE2I:SUMO thioester conjugate. The rates of some reactions are further enhanced by the action of other E3 ligases such as RANBP2. These E3 ligases catalyze SUMO transfer to substrate by one of two basic mechanisms: they interact with both the substrate and UBE2I:SUMO thus bringing them into proximity or they enhance the release of SUMO from UBE2I to the substrate.
In the cell SUMO1 is mainly concentrated at the nuclear membrane and in nuclear bodies. Most SUMO1 is conjugated to RANGAP1 near the nuclear pore. SUMO2 is at least partially cytosolic and SUMO3 is located mainly in nuclear bodies. Most SUMO2 and SUMO3 is unconjugated in unstressed cells and becomes conjugated to target proteins in response to stress (Golebiowski et al. 2009). Especially notable is the requirement for recruitment of SUMO to sites of DNA damage where conjugation to targets seems to coordinate the repair process (Flotho and Melchior 2013).
Several effects of SUMOylation have been described: steric interference with protein-protein interactions, interference with other post-translational modifications such as ubiquitinylation and phosphorylation, and recruitment of proteins that possess a SUMO-interacting motif (SIM) (reviewed in Zhao 2007, Flotho and Melchior 2013, Jentsch and Psakhye 2013, Yang and Chiang 2013). In most cases SUMOylation inhibits the activity of the target protein.
The SUMOylation reactions included in this module have met two criteria: They have been verified by assays of individual proteins (as opposed to mass proteomic assays) and the effect of SUMOylation on the function of the target protein has been tested.

Literature References

PubMed ID	Title	Journal	Year
22811915	Strategies to Identify Recognition Signals and Targets of SUMOylation Lang, V, Lopitz-Otsoa, F, Matthiesen, R, Rodriguez, MS, Da Silva-Ferrada, E	Biochem Res Int	2012
20674646	Post-translational modification by SUMO Hay, RT, Hannoun, Z, Jaffray, E, Greenhough, S, Hay, DC	Toxicology	2010
24273646	Sumoylation in gene regulation, human disease, and therapeutic action Yang, XJ, Chiang, CM	F1000Prime Rep	2013
23277067	Sumo paralogs: redundancy and divergencies Chiocca, S, Citro, S	Front Biosci (Schol Ed)	2013
24016193	Control of Nuclear Activities by Substrate-Selective and Protein-Group SUMOylation Psakhye, I, Jentsch, S	Annu. Rev. Genet.	2013
21102611	The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition Gareau, JR, Lima, CD	Nat. Rev. Mol. Cell Biol.	2010
19471022	System-wide changes to SUMO modifications in response to heat shock Tatham, MH, Cole, C, Golebiowski, F, Hay, RT, Cox, J, Nakamura, A, Barton, GJ, Matic, I, Yin, Y, Mann, M	Sci Signal	2009
23746258	Sumoylation: a regulatory protein modification in health and disease Melchior, F, Flotho, A	Annu. Rev. Biochem.	2013
23503365	Detecting endogenous SUMO targets in mammalian cells and tissues Karaca, S, Hsiao, HH, Herzig, S, Barysch, SV, Dittner, C, Melchior, F, Urlaub, H, Becker, J, Berriel Diaz, M	Nat. Struct. Mol. Biol.	2013
21693764	Comparative proteomic analysis identifies a role for SUMO in protein quality control Tatham, MH, Hay, RT, Matic, I, Mann, M	Sci Signal	2011
21252943	Purification and identification of endogenous polySUMO conjugates Tatham, MH, Bruderer, R, Hay, RT, Garg, AK, Plechanovova, A, Matic, I	EMBO Rep.	2011
17763827	Sumoylation regulates diverse biological processes Zhao, J	Cell. Mol. Life Sci.	2007
17000644	Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics Andersen, JS, Hay, RT, Ogg, SC, Lamond, AI, Vertegaal, AC, Mann, M	Mol. Cell Proteomics	2006