Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

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Citation

Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML

Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23.

PubMed ID
28112733 [ View in PubMed
]
Abstract

Small ubiquitin-like modifiers (SUMOs) are post-translational modifications (PTMs) that regulate nuclear cellular processes. Here we used an augmented K0-SUMO proteomics strategy to identify 40,765 SUMO acceptor sites and quantify their fractional contribution for 6,747 human proteins. Structural-predictive analyses revealed that lysines residing in disordered regions are preferentially targeted by SUMO, in notable contrast to other widespread lysine modifications. In our data set, we identified 807 SUMOylated peptides that were co-modified by phosphorylation, along with dozens of SUMOylated peptides that were co-modified by ubiquitylation, acetylation and methylation. Notably, 9% of the identified SUMOylome occurred proximal to phosphorylation, and numerous SUMOylation sites were found to be fully dependent on prior phosphorylation events. SUMO-proximal phosphorylation occurred primarily in a proline-directed manner, and inhibition of cyclin-dependent kinases dynamically affected co-modification. Collectively, we present a comprehensive analysis of the SUMOylated proteome, uncovering the structural preferences for SUMO and providing system-wide evidence for a remarkable degree of cross-talk between SUMOylation and other major PTMs.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Histone deacetylase 5Q9UQL6Details
Jun dimerization protein 2Q8WYK2Details
Cyclic AMP-dependent transcription factor ATF-1P18846Details
Cyclic AMP-dependent transcription factor ATF-3P18847Details
Cyclic AMP-dependent transcription factor ATF-4P18848Details
Cyclic AMP-dependent transcription factor ATF-6 alphaP18850Details
Survival motor neuron proteinB4DP61Details
Probable ATP-dependent RNA helicase DDX5P17844Details
Splicing factor 3B subunit 1O75533Details
Homeodomain-interacting protein kinase 2Q9H2X6Details
Homeodomain-interacting protein kinase 3Q9H422Details
Serine/threonine-protein kinase PRP4 homologQ13523Details
Histone-lysine N-methyltransferase EZH2Q15910Details
Histone-lysine N-methyltransferase EZH1Q92800Details
DNA (cytosine-5)-methyltransferase 3AQ9Y6K1Details
DNA (cytosine-5)-methyltransferase 3BQ9UBC3Details
Runt-related transcription factor 2Q13950Details
Lysine-specific histone demethylase 1AO60341Details