Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
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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
Name UniProt ID Histone deacetylase 5 Q9UQL6 Details Jun dimerization protein 2 Q8WYK2 Details Cyclic AMP-dependent transcription factor ATF-1 P18846 Details Cyclic AMP-dependent transcription factor ATF-3 P18847 Details Cyclic AMP-dependent transcription factor ATF-4 P18848 Details Cyclic AMP-dependent transcription factor ATF-6 alpha P18850 Details Survival motor neuron protein B4DP61 Details Probable ATP-dependent RNA helicase DDX5 P17844 Details Splicing factor 3B subunit 1 O75533 Details Homeodomain-interacting protein kinase 2 Q9H2X6 Details Homeodomain-interacting protein kinase 3 Q9H422 Details Serine/threonine-protein kinase PRP4 homolog Q13523 Details Histone-lysine N-methyltransferase EZH2 Q15910 Details Histone-lysine N-methyltransferase EZH1 Q92800 Details DNA (cytosine-5)-methyltransferase 3A Q9Y6K1 Details DNA (cytosine-5)-methyltransferase 3B Q9UBC3 Details Runt-related transcription factor 2 Q13950 Details Lysine-specific histone demethylase 1A O60341 Details Signal transducer and activator of transcription 1-alpha/beta P42224 Details Proliferation marker protein Ki-67 P46013 Details ELAV-like protein 1 Q15717 Details